Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

A Universal Decline Law of Classical Novae

We calculate many different nova light curves for a variety of white dwarf masses and chemical compositions, with the assumption that free-free emission from optically thin ejecta dominates the continuum flux. We show that all these light curves are homologous and a universal law can be derived by introducing a ``time scaling factor.'' The template light curve for the universal law has a slope of the flux, F \propto t^{-1.75}, in the middle part (from ~2 to ~6 mag below the optical maximum), but it declines more steeply, F \propto t^{-3.5}, in the later part (from ~6 to ~10 mag). This break on the light curve is due to a quick decrease in the wind mass-loss rate. The nova evolutions are approximately scaled by the time of break. Once the time of break is observationally determined, we can derive the various timescales of novae such as the period of a UV burst phase, the duration of optically thick wind phase, and the turnoff date of hydrogen shell-burning. We have applied our template light curve model to the three well-observed novae, V1500 Cyg, V1668 Cyg, and V1974 Cyg. Our theoretical light curves show excellent agreement with the optical y and infrared J, H, K light curves. The WD mass is estimated, from the light curve fitting, to be 1.15 M_\sun for V1500 Cyg, 0.95 ~M_\sun for V1668 Cyg, and 0.95-1.05 M_\sun for V1974 Cyg.Comment: To appear in ApJS, vol.167, 23 pages including 24 figure

Desarrollo, subjetividad y transgresiones identitarias en las costas del sur- austral chileno

This work is part of an investigation into the contemporary dynamics of development and modernization in the southern and far southern coastal areas of Chile, specifically the shoreline of the northern part of the Aysen Region. The objective is to propose a theoretical-conceptual reflection to enable ethnographic data to be framed as a problem and interpreted as a function of a political reading which - why not say so? - could transform the world of the southern and far southern coastal zone. The central argument of the text is hypothetical: the dilemmas of development, in the current circumstances of the coasts of the Aysen Region, are susceptible of resolution (at least up to a point) from a conscious, reflexive change of perspective on culture as the word is understood in anthropology. Este trabajo se enmarca en una investigación sobre las dinámicas contemporáneas del desarrollo y la modernización en las costas sur-australes de Chile, específicamente en el litoral norte de la región de Aisén. A partir de un conjunto de datos etnográficos se propone una reflexión teórico-conceptual que permita problematizar e interpretar esos datos en función de una lectura política y, por qué no decirlo, transformadora del mundo costero sur-austral. El argumento central del texto tiene carácter hipotético: las encrucijadas del desarrollo, en las actuales coyunturas de las costas aiseninas, son susceptibles de ser resueltas (al menos hasta cierto punto) a partir de un giro reflexivo y consciente sobre eso que en antropología llamamos cultura

The Application of Foreign Law by Judicial and Non-Judicial Authorities - The Netherlands

De bescherming van fundamentele rechten in een integrerend Europ

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning

Prevalence and consequences of patient safety incidents in general practice in the Netherlands: a retrospective medical record review study

Contains fulltext : 97252.pdf (publisher's version ) (Open Access)BACKGROUND: Patient safety can be at stake in both hospital and general practice settings. While severe patient safety incidents have been described, quantitative studies in large samples of patients in general practice are rare. This study aimed to assess patient safety in general practice, and to show areas where potential improvements could be implemented. METHODS: We conducted a retrospective review of patient records in Dutch general practice. A random sample of 1,000 patients from 20 general practices was obtained. The number of patient safety incidents that occurred in a one-year period, their perceived underlying causes, and impact on patients' health were recorded. RESULTS: We identified 211 patient safety incidents across a period of one year (95% CI: 185 until 241). A variety of types of incidents, perceived causes and consequences were found. A total of 58 patient safety incidents affected patients; seven were associated with hospital admission; none resulted in permanent disability or death. CONCLUSIONS: Although this large audit of medical records in general practices identified many patient safety incidents, only a few had a major impact on patients' health. Improving patient safety in this low-risk environment poses specific challenges, given the high numbers of patients and contacts in general practice

Leadership, staffing and quality of care in nursing homes

<p>Abstract</p> <p>Background</p> <p>Leadership and staffing are recognised as important factors for quality of care. This study examines the effects of ward leaders' task- and relationship-oriented leadership styles, staffing levels, ratio of registered nurses and ratio of unlicensed staff on three independent measures of quality of care.</p> <p>Methods</p> <p>A cross-sectional survey of forty nursing home wards throughout Norway was used to collect the data. Five sources of data were utilised: self-report questionnaires to 444 employees, interviews with and questionnaires to 13 nursing home directors and 40 ward managers, telephone interviews with 378 relatives and 900 hours of field observations. Separate multi-level analyses were conducted for quality of care assessed by relatives, staff and field observations respectively.</p> <p>Results</p> <p>Task-oriented leadership style had a significant positive relationship with two of the three quality of care indexes. In contrast, relationship-oriented leadership style was not significantly related to any of the indexes. The lack of significant effect for relationship-oriented leadership style was due to a strong correlation between the two leadership styles (<it>r </it>= 0.78). Staffing levels and ratio of registered nurses were not significantly related to any of the quality of care indexes. The ratio of unlicensed staff, however, showed a significant negative relationship to quality as assessed by relatives and field observations, but not to quality as assessed by staff.</p> <p>Conclusions</p> <p>Leaders in nursing homes should focus on active leadership and particularly task-oriented behaviour like structure, coordination, clarifying of staff roles and monitoring of operations to increase quality of care. Furthermore, nursing homes should minimize use of unlicensed staff and address factors related to high ratios of unlicensed staff, like low staff stability. The study indicates, however, that the relationship between staffing levels, ratio of registered nurses and quality of care is complex. Increasing staffing levels or the ratio of registered nurses alone is not likely sufficient for increasing quality of care.</p

Mental fatigue after very severe closed head injury: Sustained performance, mental effort, and distress at two levels of work-load in a driving simulator

In patients with very severe closed head injury (CHI), returning to work is often problematic. The present study focuses on a persistent complaint of these patients, viz. mental fatigue. To study this, the effect of sustained workload is assessed in a continuous dynamic divided attention task. Three types of measures are employed: performance loss with time-on-task, and subjective reports and cardiovascular measures of mental effort and distress. Eight very severe CHI patients (mean post-traumatic amnesia duration 51 days, mean age 23 years, (SD 6.4) and eight hospital controls (mean age 29 years, (SD 5.9) were tested. No differences were found between the patients and controls in the effects of task load on performance and the amount of mental effort, even in very demanding simulated work conditions. This parallels previous findings in less demanding laboratory tasks of sustained attention. Effects of CHI were found on both subjective and physiological indicators of distress. Compared to the controls, patients showed stronger effects on systolic blood pressure and subjectively experienced load