Legal Aspects of the Teacher Tenure Laws

The purpose of this study has been to discover those guiding principles which have been followed in the laws of those states having permanent teacher tenure legislation as such principles have manifested themselves in the work of the legislators who framed the laws and in the decisions of the courts which have given them judicial interpretation

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

A bedtime milk snack does not impact resting metabolic rate, substrate utilisation, and appetite the following morning in mildly overweight males

Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) of protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24.3 (SEM 0.8) years; BMI: 27.4 (SEM 1.1) kg/m2). Next morning measurements of resting metabolic rate (RMR), appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (SEM 276) kJ/day, BS10: 7482 (SEM 262) kJ/day, BS30: 7851 (SEM 261) kJ/day, P = 0.19) or substrate utilisation as measured by respiratory exchange ratio (P = 0.64). Bedtime milk ingestion reduced hunger (P = 0.01) and increased fullness (P = 0.04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (SEM 365) kJ, BS10: 2070 (SEM 336) kJ, BS30: 2582 (SEM 384) kJ, P = 0.21) and 24 h post-trial (P = 0.95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared to a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management

Quantum computing accelerator I/O : LDRD 52750 final report.

In a superposition of quantum states, a bit can be in both the states '0' and '1' at the same time. This feature of the quantum bit or qubit has no parallel in classical systems. Currently, quantum computers consisting of 4 to 7 qubits in a 'quantum computing register' have been built. Innovative algorithms suited to quantum computing are now beginning to emerge, applicable to sorting and cryptanalysis, and other applications. A framework for overcoming slightly inaccurate quantum gate interactions and for causing quantum states to survive interactions with surrounding environment is emerging, called quantum error correction. Thus there is the potential for rapid advances in this field. Although quantum information processing can be applied to secure communication links (quantum cryptography) and to crack conventional cryptosystems, the first few computing applications will likely involve a 'quantum computing accelerator' similar to a 'floating point arithmetic accelerator' interfaced to a conventional Von Neumann computer architecture. This research is to develop a roadmap for applying Sandia's capabilities to the solution of some of the problems associated with maintaining quantum information, and with getting data into and out of such a 'quantum computing accelerator'. We propose to focus this work on 'quantum I/O technologies' by applying quantum optics on semiconductor nanostructures to leverage Sandia's expertise in semiconductor microelectronic/photonic fabrication techniques, as well as its expertise in information theory, processing, and algorithms. The work will be guided by understanding of practical requirements of computing and communication architectures. This effort will incorporate ongoing collaboration between 9000, 6000 and 1000 and between junior and senior personnel. Follow-on work to fabricate and evaluate appropriate experimental nano/microstructures will be proposed as a result of this work

A bedtime milk snack does not impact resting metabolic rate, substrate utilisation, and appetite the following morning in mildly overweight males

Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) of protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24.3 (SEM 0.8) years; BMI: 27.4 (SEM 1.1) kg/m2). Next morning measurements of resting metabolic rate (RMR), appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (SEM 276) kJ/day, BS10: 7482 (SEM 262) kJ/day, BS30: 7851 (SEM 261) kJ/day, P = 0.19) or substrate utilisation as measured by respiratory exchange ratio (P = 0.64). Bedtime milk ingestion reduced hunger (P = 0.01) and increased fullness (P = 0.04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (SEM 365) kJ, BS10: 2070 (SEM 336) kJ, BS30: 2582 (SEM 384) kJ, P = 0.21) and 24 h post-trial (P = 0.95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared to a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management

Challenges in Columbia River Fisheries Conservation: A Response to Duda et al.

The salmonid fisheries of the Columbia River Basin (CRB) have enormous socioeconomic, cultural, and ecological importance to numerous diverse stakeholders (eg state, federal, tribal, nonprofit), and there are a wide array of opinions and perspectives on how these fisheries should be managed. Although we appreciate Duda et al.\u27s commentary, it offers only one perspective of many in this context. The objective of our paper (Hand et al. 2018) was to provide justification for “the importance of social–ecological perspectives when communicating conservation values and goals, and the role of independent science in guiding management policy and practice for salmonids in the CRB”. However, we did not intend to strictly advocate for a single course of action, and the available space within our paper\u27s Panel 1 limited us from engaging in a thorough ecological debate

Reflections on the labyrinth: Investigating Black and Minority Ethnic leaders’ career experiences

Black and Minority Ethnic (BME) employees appear to experience more difficulty reaching senior leadership positions than their white counterparts. Using Eagly and Carli’s (2007) metaphor of the labyrinth our aim was to give voice to black and minority ethnic managers who have successfully achieved senior management roles, and compare their leadership journeys with those of matched white managers. This paper used semi-structured interviews and attribution theory to examine how 20 black and minority ethnic and 20 white senior managers, from a UK government department made sense of significant career incidents in their leadership journeys. Template analysis was used to identify facilitators and barriers of career progression from causal explanations of these incidents. Although BME and white managers identified four common themes (visibility, networks, development, and line manager support), they differed in how they made sense of formal and informal organisational processes to achieve career progression. The findings are used to theorise about the individual and organisational factors that contribute to the leadership journeys of minority ethnic employees

New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Draft Genome of the Filarial Nematode Parasite \u3ci\u3eBrugia malayi\u3c/i\u3e

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design