Characterization and Scaling of MOS Flip Flop Performance in Synchronizer Applications

The measured and calculated values of t he Flip Flop parameters needed to specify synchronizer reliability are presented for 3 different depletion-load, silicon gate, NMOS, R-S Flip Flop circuits with gate lengths ranging from 6μm to 4.2μm. Estimates of the probability of synchronizer failure to resolve within allowed or desired times can be determined from these parameters

A noncanonical PWI domain in the N-terminal helicase-associated region of the spliceosomal Brr2 protein

The spliceosomal RNA helicase Brr2 is required for the assembly of a catalytically active spliceosome on a messenger RNA precursor. Brr2 exhibits an unusual organization with tandem helicase units, each comprising dual RecA-like domains and a Sec63 homology unit, preceded by a more than 400-residue N-terminal helicase-associated region. Whereas recent crystal structures have provided insights into the molecular architecture and regulation of the Brr2 helicase region, little is known about the structural organization and function of its N-terminal part. Here, a near-atomic resolution crystal structure of a PWI-like domain that resides in the N-terminal region of Chaetomium thermophilum Brr2 is presented. CD spectroscopic studies suggested that this domain is conserved in the yeast and human Brr2 orthologues. Although canonical PWI domains act as low-specificity nucleic acid-binding domains, no significant affinity of the unusual PWI domain of Brr2 for a broad spectrum of DNAs and RNAs was detected in band-shift assays. Consistently, the C. thermophilum Brr2 PWI-like domain, in the conformation seen in the present crystal structure, lacks an expanded positively charged surface patch as observed in at least one canonical, nucleic acid-binding PWI domain. Instead, in a comprehensive yeast two-hybrid screen against human spliceosomal proteins, fragments of the N-terminal region of human Brr2 were found to interact with several other spliceosomal proteins. At least one of these interactions, with the Prp19 complex protein SPF27, depended on the presence of the PWI-like domain. The results suggest that the N-terminal region of Brr2 serves as a versatile protein-protein interaction platform in the spliceosome and that some interactions require or are reinforced by the PWI-like domain

Public Benefits of Undeveloped Lands on Urban Outskirts: Non-Market Valuation Studies and their Role in Land Use Plans

Over the past three decades, the economics profession has developed methods for estimating the public benefits of green spaces, providing an opportunity to incorporate such information into land-use planning. While federal regulations routinely require such estimates for major regulations, the extent to which they are used in local land use plans is not clear. This paper reviews the literature on public values for lands on urban outskirts, not just to survey their methods or empirical findings, but to evaluate the role they have played--or have the potential to play-- in actual land use plans. Based on interviews with authors and representatives of funding agencies and local land trusts, it appears that academic work has had a mixed reception in the policy world. Reasons for this include a lack of interest in making academic work accessible to policy makers, emphasizing revealed preference methods which are inconsistent with policy priorities related to nonuse values, and emphasis on benefit-cost analyses. Nevertheless, there are examples of success stories that illustrate how such information can play a vital role in the design of conservation policies. Working Paper 07-2

In-Air Evoked Potential Audiometry of Grey Seals (Halichoerus grypus) from the North and Baltic Seas

In-air anthropogenic sound has the potential to affect grey seal (Halichoerus grypus) behaviour and interfere with acoustic communication. In this study, a new method was used to deliver acoustic signals to grey seals as part of an in-air hearing assessment. Using in-ear headphones with adapted ear inserts allowed for the measurement of auditory brainstem responses (ABR) on sedated grey seals exposed to 5-cycle (2-1-2) tone pips. Thresholds were measured at 10 frequencies between 1–20 kHz. Measurements were made using subcutaneous electrodes on wild seals from the Baltic and North Seas. Thresholds were determined by both visual and statistical approaches (single point F-test) and good agreement was obtained between the results using both methods. The mean auditory thresholds were ≤40 dB re 20 µPa peak equivalent sound pressure level (peSPL) between 4–20 kHz and showed similar patterns to in-air behavioural hearing tests of other phocid seals between 3 and 20 kHz. Below 3 kHz, a steep reduction in hearing sensitivity was observed, which differed from the rate of decline in sensitivity obtained in behavioural studies on other phocids. Differences in the rate of decline may reflect influence of the ear inserts on the ability to reliably transmit lower frequencies or interference from the structure of the distal end of the ear canal

Hallermann-Streiff Syndrome: No Evidence for a Link to Laminopathies

Hallermann-Streiff syndrome (HSS) is a rare inherited disorder characterized by malformations of the cranium and facial bones, congenital cataracts, microphthalmia, skin atrophy, hypotrichosis, proportionate short stature, teeth abnormalities, and a typical facial appearance with prominent forehead, small pointed nose, and micrognathia. The genetic cause of this developmental disorder is presently unknown. Here we describe 8 new patients with a phenotype of HSS. Individuals with HSS present with clinical features overlapping with some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia (MAD). HGPS is caused by de novo point mutations in the LMNA gene, coding for the nuclear lamina proteins lamin A and C. MAD with type A and B lipodystrophy are recessive disorders resulting from mutations in LMNA and ZMPSTE24 , respectively. ZMPSTE24 in addition to ICMT encode proteins involved in posttranslational processing of lamin A. We hypothesized that HSS is an allelic disorder to HGPS and MAD. As the nuclear shape is often irregular in patients with LMNA mutations, we first analyzed the nuclear morphology in skin fibroblasts of patients with HSS, but could not identify any abnormality. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in the 8 patients with HSS revealed the heterozygous missense mutation c.1930C>T (p.R644C) in LMNA in 1 female. Extreme phenotypic diversity and low penetrance have been associated with the p.R644C mutation. In ZMPSTE24 and ICMT , no pathogenic sequence change was detected in patients with HSS. Together, we found no evidence that HSS is another laminopathy

Electron correlation vs. stabilization: A two-electron model atom in an intense laser pulse

We study numerically stabilization against ionization of a fully correlated two-electron model atom in an intense laser pulse. We concentrate on two frequency regimes: very high frequency, where the photon energy exceeds both, the ionization potential of the outer {\em and} the inner electron, and an intermediate frequency where, from a ``single active electron''-point of view the outer electron is expected to stabilize but the inner one is not. Our results reveal that correlation reduces stabilization when compared to results from single active electron-calculations. However, despite this destabilizing effect of electron correlation we still observe a decreasing ionization probability within a certain intensity domain in the high-frequency case. We compare our results from the fully correlated simulations with those from simpler, approximate models. This is useful for future work on ``real'' more-than-one electron atoms, not yet accessible to numerical {\em ab initio} methods.Comment: 8 pages, 8 figures in an extra ps-file, submitted to Phys. Rev. A, updated references and shortened introductio

Insight out : making creativity visible

Models of creative problem solving are predicated upon mental states to explain everything from the outcome of problem‐solving experiments to the emergence of artistic creativity. We present two converging perspectives that describe a profoundly different ontological description of creativity. Our analysis proceeds from a distinction between first‐order problem solving, where the agent interacts with a physical model of the problem and second‐order problem solving, where the agent must cogitate a solution to a problem that is presented as a verbal description of a state of the world but where the agent does not or cannot transform physical elements of a problem. We acknowledge the recent evidence that foregrounds the importance of working memory in problem solving, including insight problem solving. However, we stress that the impressive psychometric success is obtained with a methodology that only measures second‐order problem solving; we question whether first‐order problem solving is equally well predicted by measures of cognitive or dispositional capacities. We propose that if mental simulation is replaced by the opportunity to engage with a physical model of a problem then the environment can provide affordances that help the participant to solve problems. In the second part of the paper, we present the subjective experience of an artist as he monitors the microdecisions that occur during the morphogenesis of a large, clay, sculptural installation. The testimony is a vivid demonstration that creative action occurs, not in the brain, but in the movement between the hand and the clay. Insight becomes outsight

Anaemia and quality of life in chronic kidney disease: A consensus document from the European Anaemia of CKD Alliance

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD