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The paper reports studies of the effects of ester side-group size and structure on chain transfer to polymer (CTP) and mol% branches (%br) in the final polymers from monomer-starved semi-batch emulsion homopolymerizations of a series of alkyl acrylates with different numbers of ester OR side-group carbon atoms (NsgC) in the range 1–10. Although the high instantaneous conversions and high gel contents in the final polymers show that intermolecular CTP is significant, the kinetics have been analysed principally in terms of intramolecular CTP (intraCTP) because this is expected to be numerically the dominant CTP process. For linear OR side groups, there is a small, continuous increase in %br (from ~ 3.4 to ~ 5.0 mol%) as NsgC increases from 1 to 8, which arises predominantly from the acrylate molar mass (Macrylate) reducing the molar monomer concentration and from the small increase in rate coefficient for propagation (kp) as NsgC increases; no discernible effects of NsgC on the rate coefficient for intraCTP ( k trP intra ) are evident. For isomeric butyl acrylates, there is no measurable effect of isomer structure on %br (4.3–4.4 mol%), indicating that butyl groups are too small for changes in side-group bulkiness to influence k trP intra and kp. A similar observation was made for n-hexyl acrylate (nHA) and 2-ethylbutyl acrylate (%br 4.7–4.8 mol%). However, cyclohexyl acrylate (cHA) gives a much higher %br (~ 7.2 mol%), which has been assigned to steric effects increasing k trP intra because kp values for nHA and cHA are very similar. For OR side-groups with NsgC of 8 and10, there is a strong effect of side-group non-linearity (2-ethylhexyl, iso-octyl and iso-decyl) increasing %br, with polymers from n-alkyl acrylates having much lower %br (~ 4.5–5.0 mol%) than those from the equivalent non-linear acrylates (~ 6.7–7.1 mol%); since the kp values are expected to be similar for these acrylates, it is evident that the much bulkier non-linear OR groups cause a significant increase in k trP intra compared to the linear equivalents. Tentative hypotheses for these steric effects have been postulated. Studies of the effect of temperature (0–80 °C) on CTP and %br for methyl acrylate solution homopolymerization (in which intraCTP should be completely dominant) show the expected reduction in %br as temperature reduces, such that CTP is negligible at 0 °C; Arrhenius analysis gives an activation energy of 40.7 kJ mol−1 for intraCTP, which is within the range of values reported for n-butyl acrylate. [ABSTRACT FROM AUTHOR]

Purpose: To assess the utility of the Manufacturer And User Facility Device Experience (MAUDE) database in objectively capturing adverse events for transvaginal mesh in the United States. Materials and Methods: We reviewed 1,103 individual medical device reports submitted to the MAUDE database that inspired the United States (US) Food and Drug Administration's 2008 Public Health Notification. Entries were compiled into a categorical database that reported manufacturer, brand, reporter type, report source, and type of adverse event. Results: There were numerous examples of missing, duplicated, and non-standardized entries. Analysis revealed 64 reports with duplicated information, and six reports representing multiple patients. Forty-seven percent of medical device reports did not identify a reporter source. At least 28% of reported devices are no longer on the US market. There was wide variability in the quality and completeness of submitted reports and true adverse event rates could not be accurately calculated because the number of total cases was unknown. Conclusions: The MAUDE database was limited in its ability to collect, quantify, and standardize real-life adverse events related to transvaginal mesh. While it functions to collect information related to isolated adverse events, systematic limitations of the MAUDE database, that no doubt extend to other medical devices, necessitate the development of new reporting systems. Alternatives are under development, which may allow regulators to more accurately scrutinize the safety profiles of specific medical devices. [ABSTRACT FROM AUTHOR]

Manufacturing variability is an increasingly significant problem. Silicon devices that are designed to be identical will display widely ranging characteristics after manufacture. Power use, supported clock frequencies and lifespan may all vary considerably. This is of particular concern for embedded systems because of their extensive use of complex system‐on‐chip (SoC)‐based architectures. If this variability is not tolerated by the software, then manufacturing yields are reduced and devices are not used efficiently. This study discusses a novel approach to the integration of variability‐mitigation techniques that uses model‐driven engineering to explicitly consider variability as part of the development process. Developers can build systems that are much more resilient to variability effects, allowing systems to have higher yields, lower costs and greater reliability. The approach uses code generation and code transformation to simplify design‐space exploration and reduce time‐to‐market. The approach is illustrated with an example of audio processing on a complex multiprocessor SoC with simulated variability, and it is shown to be increasingly effective as system variability becomes more significant. [ABSTRACT FROM AUTHOR]

The colonies of Australia built land transport to enable the production and export of agricultural products to Britain. Railways focused commerce on the colonial, later state, capital cities. Administration of roads and railways has been centralised in the state capitals, despite the increasing influence of the commonwealth (national) government since federation in 1901. Centralisation is conceptualised in terms of political control, government administration and the spatial concentration of industry. It has been facilitated by the administrative structure of government-owned and operated railways and a very fragmented system of local government. The rise of road transport has seen some large organisations emerge outside the state capitals, but the industry remains highly dispersed. These observations are based on secondary sources. They are used to reinterpret Australian regional land transport history to help explain the continuing weakness of regional institutions in transport administration and prompt consideration of the breadth of change required to establish non-metropolitan regional transport planning. [ABSTRACT FROM AUTHOR]

Abstract: Monosaccharides are selectively converted to monobenzoates in a base-catalyzed reaction with benzoyl methyl phosphate (BzMP) and a lanthanum salt in water. Yields are reported in terms of formation of the ester, which competes with hydrolysis of BzMP, to give an estimate of the efficiency of the conversion of the sugar. Higher conversions can be achieved using excess reagent. Regioselectivity is influenced by the structure of the glycoside. For example, the reaction leads to different product distributions from α- and β-anomers of the glycosides. The reaction combination provides a basis for efficient ester formation in specific geometric situations, providing a means of identification as well as modification. [Copyright &y& Elsevier]

In this paper it is shown that if a graph G possesses a spanning subgraph H with a strong vertex magic total labeling (VMTL) and G - E(H) is even-regular, then G also has a strong VMTL. Among other things, this is used to conclude that all Hamiltonian regular graphs of odd order possess strong VMTLs. A relationship is then demonstrated between regular graphs of even degree and sparse magic squares. We next consider cubic graphs of order 2n consisting of two 2-factors of order n, connected by a 1-factor (quasi-prisms). Based on McQuillan's construction of VMTLs of such 3-regular graphs, VMTLs are derived for similar regular graphs of any odd degree. Finally, a construction is given for VMTLs of quartic graphs of order 4n + 2 consisting of two cycles of odd order n connected by a 2-factor (simple quasi-anti-prisms), and based on this construction VMTLs are derived for similar regular graphs of any even degree. [ABSTRACT FROM AUTHOR]

It was previously reported that diols dissolved in water (pH 8, EPPS buffer) react with benzoyl methyl phosphate (BMP) in the presence of lanthanide ions to form monobenzoyl esters. We have investigated the possibility of extending this process to include formation of esters of monosaccharides in water from lanthanide-catlayzed reactions with BMP. The combination of methyl-α-D-glucopyranoside and BMP in the presence of lanthanum trichloride gave selective monoacylation of the 2- and 6-hydroxyl groups in a ratio of 2:1. The likely mechanism involves preferential bisbidentate coordination of BMP and the diol to lanthanide ion (which explains how an ester forms when water is in enormous excess) followed by base-catalyzed intramolecular acyl transfer. The method should be generally applicable where a selective acylation reaction in water as solvent is desirable. [ABSTRACT FROM AUTHOR]

The synthesis, organic reactivity, and metal-complex formation of interesting (RP) x Se y heterocycles is reviewed. These heterocycles can now be accessed through a variety of means including the simple use of elemental selenium, Ph3PSe, and the versatile (PhP)4Se. These and other reagents have now been used to make a remarkable array of P?–?Se heterocycles. For example, cyclic systems with, PSe4, P2Se2, CP2Se and C P2Se2 are described. Many of these compounds have been authenticated with crystal structures revealing unusual features in the structures and bonding. Interest in these compounds has grown substantially in recent years, since selenium has been found to be an essential part of some biologically active molecules and is an essential nutrient for mammals and prevents necrotic degeneration of the liver, heart, and other organs. Moreover, organoselenium compounds have been reported to have potential pharmaceutical properties especially when incorporated into biological compounds. [ABSTRACT FROM AUTHOR]

Small regional communities are having widely different experiences of globalisation but many share dependent relations with corporations and governments. Those which are under threat are often finding themselves dependent on their own resources, including the leadership of local people. This article compares the interpretations of change and the experiences of local leaders in two geographically and historically diverse situations. It finds that despite such diversity, there are similarities of experience. It concludes with some consideration given to state policy regarding community leadership, tempering a view that leadership can provide solutions to regional decline. [ABSTRACT FROM AUTHOR]

McGoldrick and Carter (2001) observe that interventions in a differentiation-based approach such as detriangling are often counterintuitive. In an attempt to understand the counterintuitive nature of a differentiation-based approach, I draw on Schnarch and others to reflect on the nature of paradox, integrity and differentiation. I discuss implications for work with a couple after violence, and I conclude that differentiation can be understood as a personal, social, or even master virtue. The paper moves backwards and forwards between a case example, and reflections on theory. [ABSTRACT FROM AUTHOR]

The results of a quality review of 89 of the 101 environmental statements (ESs) pertaining to the British forest sector over the period 1988-1998 are presented. The methodology was based on the Environmental Statement Review Package, modified for the forest sector. The standard of ESs was generally poor, only one being wholly acceptable. The ESs presented limited useful additional information to decision makers. A fundamental, recurrent issue was the failure to adequately scope assessments, leading to unfocused baseline data collection, inadequate identification of impacts, and inappropriate or inadequate determination of impact significance. Given that wholesale amendments to environmental impact assessment (EIA) legislation are unlikely in the near future, it is up to the Forestry Commission (as the competent authority) to bring about improvements in the quality of ESs. This may be achieved by providing further guidelines on the EIA process, particularly screening and scoping, and by introducing a consistent UK-wide ES review system for forestry projects. [ABSTRACT FROM AUTHOR]

A unique collaborative, sociological study undertaken during 1995-7, explored the social construction of drought as a disaster, looking at farm families in two Australian states: Queensland (beef producers) and New South Wales (sheep/wheat producers). A decision was made to interview the women and men separately to test our hypothesis that there would be gender issues in any analysis of a disaster, but particularly one which has had so much long-term impact on individuals, families and communities, such as drought, Interviews were conducted with over 100 individuals male and female. We conclude that drought as a disaster is a gendered experience. The paper draws on the narratives of some women involved in the study to identify 'themes of difference' which confirm the necessity to maintain gender as a variable in all studies of the social impacts of disaster. [ABSTRACT FROM AUTHOR]

Extension theory has moved towards conceptualizations which illuminate the power relationships inherent in extension practice. Consideration of power relationships raises questions about the interests of the parties involved and problems inherent in their conceptualization. Extension theory has not yet tackled these problems, leaving the ‘farmer first’ and ‘beyond farmer first’ approaches as well as earlier top-down models inadequate. This paper discusses the relationship between concepts of power and interests before raising some problems implied by interests. While interests are seen as essentially contestable and their assessment is seen as cultural construction, their analysis can be based on a pragmatic approach to human needs. A model which sees extension as a power relationship steers it towards outcomes which emphasize the enactment of power relations rather than behavioural objectives. The objective for extension becomes creation of a pluralistic arena in which the assessment of interests of all parties is challengeable and is challenged by all others. [ABSTRACT FROM AUTHOR]

Australian farms continue to suffer economic pressure which directly and indirectly produces stress among farm family members. This study uses qualitative and quantitative data to isolate factors which predict stress. Financial condition, perception of what is at stake, the combination of on-farm and off-farm obligations and the general frustrations of farm life are found to predict stress among both men and women. Gender relations and attachment to farm life emerge as stronger predictors for women, while youth is a stronger predictor for men. The study concludes that attempts to develop and preserve the family farm may be creating stressful situations which threaten the family relations upon which the farming system is based. [ABSTRACT FROM AUTHOR]

N-methyl-d-aspartate (NMDA) receptor hypofunctionality is a well-studied hypothesis for schizophrenia pathophysiology, and daily dosing of the NMDA receptor co-agonist, d-serine, in clinical trials has shown positive effects in patients. Therefore, inhibition of d-amino acid oxidase (DAAO) has the potential to be a new therapeutic approach for the treatment of schizophrenia. TAK-831 (luvadaxistat), a novel, highly potent inhibitor of DAAO, significantly increases d-serine levels in the rodent brain, plasma, and cerebrospinal fluid. This study shows luvadaxistat to be efficacious in animal tests of cognition and in a translational animal model for cognitive impairment in schizophrenia. This is demonstrated when luvadaxistat is dosed alone and in conjunction with a typical antipsychotic. When dosed chronically, there is a suggestion of change in synaptic plasticity as seen by a leftward shift in the maximum efficacious dose in several studies. This is suggestive of enhanced activation of NMDA receptors in the brain and confirmed by modulation of long-term potentiation after chronic dosing. DAAO is highly expressed in the cerebellum, an area of increasing interest for schizophrenia, and luvadaxistat was shown to be efficacious in a cerebellar-dependent associative learning task. While luvadaxistat ameliorated the deficit seen in sociability in two different negative symptom tests of social interaction, it failed to show an effect in endpoints of negative symptoms in clinical trials. These results suggest that luvadaxistat potentially could be used to improve cognitive impairment in patients with schizophrenia, which is not well addressed with current antipsychotic medications. [ABSTRACT FROM AUTHOR]

Analyzes the synthesis of phosphonodithioato and phosphonodiselenaoato metal complexes by the ring opening of Ferrocenyl Lawessons and Woollins reagents respectively.. Chemical structure of the metal complexes.

Oxo-stabilised phosphonium ylides are found to form crystalline hydrogen-bonded adducts with aromatic carboxylic acids, as confirmed by X-ray diffraction. There is also strong hydrogen bonding in solution as indicated by 13C NMR spectroscopy and this confirmed adduct formation with acetic acid, benzamide, thiobenzamide, benzyl alcohol, benzenesulfinic acid and diphenylphosphinic acid. The X-ray structure of the benzamide adduct was also determined, showing a hydrogen-bonded dimeric structure. A bis(stabilised ylide) was also prepared and is found to form a complex hydrogen-bonded adduct with benzoic acid, ethanol and water. [ABSTRACT FROM AUTHOR]

Early analyses revealed that dark web marketplaces (DWMs) started offering COVID-19 related products (e.g., masks and COVID-19 tests) as soon as the COVID-19 pandemic started, when these goods were in shortage in the traditional economy. Here, we broaden the scope and depth of previous investigations by considering how DWMs responded to an ongoing pandemic after the initial shock. Our dataset contains listings from 194 DWMs collected until July 2021. We start by focusing on vaccines. We find 248 listings offering approved vaccines, like Pfizer/BioNTech and AstraZeneca, as well as vendors offering fabricated proofs of vaccination and COVID-19 passports. Then, we consider COVID-19 related products. We show that, as the regular economy has become able to satisfy the demand of these goods, DWMs have decreased their offer. Next, we analyse the profile of vendors of COVID-19 related products and vaccines. We find that most of them are specialized in a single type of listings and are willing to ship worldwide. Finally, we consider a broader set of listings mentioning COVID-19, in order to assess the general impact of the pandemic on the broader activity of DWMs. Among 10,330 such listings, we show that recreational drugs are the most affected among traditional DWMs product, with COVID-19 mentions steadily increasing since March 2020. We anticipate that our results will be of interest to researchers, practitioners, and law enforcement agencies focused on the study and safeguard of public health. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted by Guangzhou Institute of Geochemistry's vice president Gan Zhang and coworkers on concentrations of polycyclic aromatic hydrocarbons (PAHs) in 36 cities of China, which shows higher PAH levels in cities that burn more coal and its impacts on air quality.

Whilst virtualization was once restricted to large-scale computing platforms, it is now widely deployed on modern embedded computing systems. This has been driven by the availability of hardware support which alleviates the performance penalties incurred by traditional software virtualization technologies. In the domain of hard real-time systems, specialist virtualization technology which respects restricted timing requirements and constraints can be deployed to allow sharing of processors. However, other aspects of the embedded system (I/O, memory, and communication) are harder to analyze. In this paper, we argue that in order to support real-time virtualization on modern embedded systems, additional system-wide hardware support is required. We propose BlueVisor, an analyzable and scalable hardware hypervisor for many-core embedded systems, which enables time-predictable CPU, memory, and I/O virtualization, as well as supporting a fast interrupt handler, and inter-VM communication. We describe the design and implementation of the real-time hypervisor, and demonstrate how a BlueVisor-based virtualization system can be leveraged to meet real-time requirements with significant improvement in system performance, and with a low-performance cost when executing different types of software. [ABSTRACT FROM AUTHOR]

Background: Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance.Methods: Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries.Results: France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data.Conclusions: This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: Several lines of evidence support a role for CCL2 (monocyte chemotactic protein-1) and its receptor CCR2 in the development of atherosclerosis. The aim of the present study was to determine the association of the CCR2 Val64Ile polymorphism with the development of coronary artery disease in the WOSCOPS study sample set. Findings: A total of 443 cases and 1003 controls from the West of Scotland Coronary Prevention Study (WOSCOPS) were genotyped for the Val64Ile polymorphism in the CCR2 gene. Genotype frequencies were compared between cases and controls. The CCR2 Val64Ile polymorphism was found not to be associated with coronary events in this study population (odds ratio 1.15, 95% CI 0.82-1.61, p = 0.41). Conclusions: This case-control study does not support an association of the CCR2 Val64Ile polymorphism with coronary artery disease in the WOSCOPS sample set and does not confirm a possible protective role for CCR2 Val64Ile in the development of coronary artery disease. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disorder of the peripheral nervous system with a probable auto-immune pathogenesis. The nature of the responsible autoantigens is unclear in most patients. We used the Western immunoblot technique to seek antibodies to peripheral nerve protein antigens. Sera from eight of 32 (25%) CIDP patients, 12 of 37 (32%) Guillain-Barré syndrome (GBS) patients, zero of 30 (0%) chronic idiopathic axonal polyneuropathy patients and two of 39 (5%) healthy control subjects contained anti-peripheral nerve protein antibodies. The frequency of such antibodies was significantly greater in both CIDP (p = 0.04) and GBS (p = 0.003) patients than in normal control subjects. For CIDP patients, there were non-significant trends for antibodies to be more common in females and in those who responded to treatment with either intravenous immunoglobulin or plasma exchange. The commonest antibodies were directed against a band at 28 kDa, resembling that labelled by a monoclonal antibody against myelin protein zero (P0). Six CIDP and seven GBS patients' sera reacted with this band. These results support the view that antibodies to myelin proteins, and especially P0, are present in the serum of some patients with CIDP and GBS. [ABSTRACT FROM AUTHOR]

Concerns have frequently been raised about equal opportunities in the short-listing and selection procedures used by clinical psychology training courses, although little evidence exists. The aim of the study is to identify factors predicting short-listing and selection to clinical psychology training courses. A prospective study of one national cohort of applicants to UK clinical psychology training (the 2000 entry cohort of 1538 applicants) was carried out. Application forms (n = 1538), references (n = 1538) and postal questionnaires (n = 396) were used to collect demographic, biographical, academic and work experience information. Relationships between these variables and short-listing or selection to training were examined using univariate odds ratios and effect sizes, and multivariate logistic regressions. Factors most strongly predictive of short-listing and selection were proxies for academic ability (post-16 education at school, degree class, involvement in postgraduate education, authoring publications), relevant educational qualifications (a degree eligible for registration into the BPS), relevant vocational experience (a greater number and range of psychology assistant posts), and positive ratings from academic and clinical psychologist experience-related referees. Short-listing and selection to clinical psychology training relies on proxy factors related to academic ability, education, vocational experience and ratings from referees. There is little evidence of direct discrimination, although certain subgroups of applicants may be disadvantaged in their opportunities to gain relevant academic qualifications and vocational experience. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Correction to: Neurochemical Research https://doi.org/10.1007/s11064-023-03956-2 The article "Luvadaxistat: A Novel Potent and Selective d-Amino Acid Oxidase Inhibitor Improves Cognitive and Social Defcits in Rodent Models for Schizophrenia", written by Rosa Fradley, Pascal Goetghebeur, David Miller, Russell Burley, Sarah Almond, Agnès Gruart i Massó, José M. Delgado García, Bin Zhu, Eimear Howley, Jo C. Neill, Ben Grayson, Philip Gaskin, Mark Carlton, Ian Gray, Jordi Serrats, and Ceri H. Davies, was originally published electronically on the publisher's internet portal (https://link.springer.com/article/10.1007/s11064-023-03956-2) on 8 June 2023 without open access. The original article can be found online at https://doi.org/10.1007/s11064-023-03956-2. [Extracted from the article]

Social media has become integral to societal discourse and play a role in shaping public engagement, particularly in democratic electoral processes. This paper addresses the pressing issue of hate speech on social media during the 2022 US midterm elections. Unlike previous research, which often relies on limited datasets and classic methodologies, we leverage Open Source Intelligence (OSINT) and Natural Language Processing (NLP) techniques to analyze Twitter data through advanced models of entity recognition, sentiment analysis, and community extraction, having persistence in Knowledge Graphs for consuming the intelligence efficiently. Results indicate that in the US midterm elections 2022, Arizona was the state that provided more content (507,551 tweets) related to a Chief Electoral Official, with 31.58% of them identified in the most aggressive cluster due to its mean attribute values of "attack on commenter" (0.7), "inflammatory" (∼ 0. 3), "attack on author" (∼ 0. 2), and "toxicity" (∼ 0. 2). The name entity recognition model also identified an association between those aggressive tweets and the previous 2020 US Presidential campaign, characterized by attacks on election officials based on conspiracy theories campaigns. Knowledge graphs contributed to understanding the concentration of attacks and connectivity between topics commonly mentioned in hate speech content. Thus, our results offer detailed insights into the actors and dynamics of online harassment in electoral contexts, illuminating the challenges posed by harassment and proposing preventive mechanisms applicable to diverse electoral processes worldwide. • Daily online violence affects vital processes like elections via hate speech. • This study analyzes 2022 US midterms' hate speech on Twitter using NLP. • Our methodology is modular and scalable for large-scale real scenarios. [ABSTRACT FROM AUTHOR]

A survey of 20 carbonyl-stabilised phosphonium ylides with recently reported X-ray structures shows a strong correlation between the C P to C O torsion angle and the value of 2 J P–CO, with high values being associated with an anti configuration and low with syn . Seven new X-ray structural determinations are reported, several for types of ylide not crystallographically characterised before, and these also conform to this pattern. The value of 2 J P–CO is then correlated with whether or not thermal extrusion of Ph 3 PO occurs to give alkynes for over 200 ylides and an empirical rule developed that the extrusion never occurs for ylides where this value is > 11 Hz. This is used to rationalise the anomalous behaviour of some trioxo ylides and cyclic ylides, two of which afford cycloalkynes, isolated after rearrangement as the isomeric 1,3-dienes. The rule also holds for a family of novel highly fluorinated ylides which afford fluorinated alkynes in good yield upon flash vacuum pyrolysis. [ABSTRACT FROM AUTHOR]

A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/−FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/−FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/−FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10−8). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe. [ABSTRACT FROM AUTHOR]

We identified two novel mouse mutants with abnormal head-shaking behavior and neural tube defects during the course of independent ENU mutagenesis experiments. The heterozygous and homozygous mutants exhibit defects in the orientation of sensory hair cells in the organ of Corti, indicating a defect in planar cell polarity. The homozygous mutants exhibit severe neural tube defects as a result of failure to initiate neural tube closure. We show that these mutants, spin cycle and crash, carry independent missense mutations within the coding region of Celsr1, encoding a large protocadherin molecule [1]. Celsr1 is one of three mammalian homologs of Drosophila flamingo/starry night, which is essential for the planar cell polarity pathway in Drosophila together with frizzled, dishevelled, prickle, strabismus/van gogh, and rhoA . The identification of mouse mutants of Celsr1 provides the first evidence for the function of the Celsr family in planar cell polarity in mammals and further supports the involvement of a planar cell polarity pathway in vertebrate neurulation. [Copyright &y& Elsevier]

Presents information on a study which demonstrated a mutant mouse model for cerebellar ataxia that develops Purkinje cell loss in a stereotypical region-specific manner. Histology and immunohistochemistry; Identification of robotic mice which develop region-specific Purkinje cell loss; Neurodegenerative changes in the robotic cerebellum.

As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics. [ABSTRACT FROM AUTHOR]

A quiz concerning a mathematical problems on a trip to the zoo.

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls. [ABSTRACT FROM AUTHOR]