Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

Contact forces in regular 3D granular pile

We present exact results for the contact forces in a three dimensional static piling of identical, stiff and frictionless spheres. The pile studied is a pyramid of equilateral triangular base (``stack of cannonballs'') with a FCC (face centered cubic) structure. We show in particular that, as for the two dimensional case, the pressure on the base of such a pile is uniform.Comment: 10 pages, 5 figure

The Association Between Impaired Awareness and Depression, Anxiety, and Apathy in Mild to Moderate Alzheimer's Disease: A Systematic Review

Objectives: Impaired awareness of cognitive and functional deficits is a common feature of Alzheimer's disease (AD). Although a lack of awareness has been suggested to be a protective factor against experiencing affective symptoms, such as depression, anxiety, and apathy which are common in AD, there is conflicting evidence about the links between them. This systematic review examines the evidence for an association between impaired awareness and depressive, anxiety, and apathy symptoms in mild to moderate AD. / Method: We searched four databases (OvidMedline, Embase, PsycInfo, and PsycArticles) using terms encompassing awareness, apathy, depression, anxiety, and mild-moderate AD. We included studies that assessed the relationship between awareness and depressive symptoms, anxiety symptoms, or apathy. We assessed included papers for quality and report results using a narrative approach, prioritizing high quality studies. / Results: We identified 1,544 articles, and twenty-seven studies fulfilled inclusion criteria (high-quality = 15; moderate-quality = 12). Most high-quality studies reported that impaired awareness in early-stage AD is cross-sectionally linked with fewer depressive symptoms and anxiety symptoms (correlation ranged from −0.3 to −0.7), but with more apathy. / Conclusions: High-quality studies suggested that in people with early AD, impaired awareness is related to fewer depressive and anxiety symptoms and to more apathy. Future research should focus on elucidating causality among impaired awareness and these symptoms in AD

Evaluating shoreline identification using optical satellite images

A technique to extract the shoreline location from optical satellite images has been developed and evaluated for the case study site of Progreso, Yucatán, México. A novel method to extract a satellite-derived shoreline (SDS) was developed ensuring the maximum contrast between sea and land. The area under investigation is an 8. km length of shoreline that faces north into the Gulf of México.The SDS was validated using quasi-simultaneous in situ shoreline measurements, both adjusted to equal water levels. In situ shoreline measurements recorded the instantaneous shoreward extent of the wave run-up when walking along the beach.The validation of SDS revealed that the SDS is located consistently seawards of the in situ shoreline, explained by: a) the water depth that optical satellite image requires to identify a pixel either as sea or land, and b) the shoreward extent of the wave run-up. The overall distance between SDS and in situ shoreline is 5.6. m on average with a standard deviation of 1.37. m (in the horizontal) over 8. km of shoreline. Confidence bounds considering the shoreward extent of the wave run-up, inter-tidal beach slope variation and tidal uncertainty were computed to assess the accuracy of the SDS.The SDS has been shown to be capable of detecting shoreline changes of less than 10. m and abrupt changes due to storms. The success of our method suggests that it should be applicable to other locations, after adapting the confidence bounds to the beach conditions

Self-organization mechanisms for the formation on nearshore crescentic and transverse sand bars

The formation and development of transverse and crescentic sand bars in the coastal marine environment has been investigated by means of a nonlinear numerical model based on the shallow-water equations and on a simpli ed sediment transport parameterization. By assuming normally approaching waves and a saturated surf zone, rhythmic patterns develop from a planar slope where random perturbations of small amplitude have been superimposed. Two types of bedforms appear: one is a crescentic bar pattern centred around the breakpoint and the other, herein modelled for the rst time, is a transverse bar pattern. The feedback mechanism related to the formation and development of the patterns can be explained by coupling the water and sediment conservation equations. Basically, the waves stir up the sediment and keep it in suspension with a certain cross-shore distribution of depth-averaged concentration. Then, a current flowing with (against) the gradient of sediment concentration produces erosion (deposition). It is shown that inside the surf zone, these currents may occur due to the wave refraction and to the redistribution of wave breaking produced by the growing bedforms. Numerical simulations have been performed in order to understand the sensitivity of the pattern formation to the parameterization and to relate the hydro-morphodynamic input conditions to which of the patterns develops. It is suggested that crescentic bar growth would be favoured by high-energy conditions and ne sediment while transverse bars would grow for milder waves and coarser sediment. In intermediate conditions mixed patterns may occur

Planning the unplannable: Scenarios on the future of space

The article of record as published may be located at http://dx.doi.org/10.1016/ j.spacepol.2009.11.007This article explores the use of scenario analysis as a methodology to rigorously analyze potential space futures, particularly with respect to space security challenges, in the context of rapid and uncertain change across several dimensions of human space activities. The successful use of scenario analysis in other (e.g. corporate and military) sectors is described and results of an initial scenario analysis workshop are presented. Scenario analysis is recommended as a promising approach to evaluating the long-term consequences of various policy choices in the context of uncertainty, and as a process well-suited to fostering communication and building consensual knowledge among diverse stakeholders

Geologic and mineral and water resources investigations in western Colorado, using Skylab EREP data

The author has identified the following significant results. Skylab photographs are superior to ERTS images for photogeologic interpretation, primarily because of improved resolution. Lithologic contacts can be detected consistently better on Skylab S190A photos than on ERTS images. Color photos are best; red and green band photos are somewhat better than color-infrared photos; infrared band photos are worst. All major geologic structures can be recognized on Skylab imagery. Large folds, even those with very gentle flexures, can be mapped accurately and with confidence. Bedding attitudes of only a few degrees are recognized; vertical exaggeration factor is about 2.5X. Mineral deposits in central Colorado may be indicated on Skylab photos by lineaments and color anomalies, but positive identification of these features is not possible. S190A stereo color photography is adequate for defining drainage divides that in turn define the boundaries and distribution of ground water recharge and discharge areas within a basin

An Initial Assessment of Remote Access Computer Laboratories for IS Education: A Multiple Case Study

New technologies are allowing universities and colleges to create remotely accessible, server-based laboratories that support the teaching of server-based software application development. However, the organizational and technical issues associated with implementing these servers often compromise the pedagogical potential of introducing server-based technologies into the classroom. The purpose of this paper is to make an initial assessment of the organizational and technical issues associated with using server-based, remote access computer labs in an academic or IT training environment. Given the investigative nature of this research, a multiple case study method is used including scripted interviews with eighteen leaders in IS education and IT training. An analysis of these cases suggests six categories of issues: (1) organizational issues with lab setup and administration, (2) technical issues with lab setup and administration, (3) cost issues related to faculty, (4) student requirements for the lab, (5) faculty/instructor requirements for the lab, and (6) employer requirements for the lab. We conclude that the major challenge in deploying a remote access computer laboratory is the development of an institutional environment where IT staff and IS faculty work together to design, implement and administer the technologies

Empathy and its associations with sociodemographic and personality characteristics in a large UK population sample

Background: Empathy is fundamental to social cognition, driving prosocial behaviour and mental health. Self-reported empathy varies across cultures and there are differing reports of associations with demographic characteristics. We therefore aimed in a UK survey to characterise two main self-reported components of empathy, namely empathic concern (feeling compassion) and perspective taking (understanding others’ perspective). We hypothesised that empathy would be associated with age, gender, ethnicity, relationship status, employment, socio-economic status, education, and personality. / Methods: We asked participants in the COVID-19 Social Study - an internet-based survey of UK-dwelling adults aged ≥18 years - to complete the Interpersonal Reactivity Index subscales measuring empathic concern and perspective taking, and sociodemographic and personality questionnaires. We weighted the sample to be UK population representative and employed multivariable weighted linear regression models. Results: In 30,033 respondents, mean empathic concern score was 3.86 (95% confidence interval 3.85, 3.88) and perspective taking was 3.57 (3.56. 3.59), the correlation between these subscores was 0.45 (p < 0.001). In adjusted models, greater empathic concern was associated with female gender, non-white ethnicity, having more education, working in health, social-care, or childcare professions, and having higher neuroticism, extroversion, openness to experience and agreeableness traits. Perspective taking was associated with younger age, female gender, more education, employment in health or social-care, neuroticism, openness, and agreeableness. / Conclusions: Women and people working in caring professions have higher empathy levels. Perspective taking declines with age but empathic concern does not. Empathic compassion and understanding are distinct dimensions of empathy with differential associations with demographic factors