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Vitamin B₁₂ (cobalamin) is one of Nature's most complex small molecules. It is a cobalt-containing modified tetrapyrrole that plays a number of key metabolic roles in many prokaryotic systems and is also essential to the biochemistry of higher animals. However, it is made by only certain bacteria, requiring around thirty enzymatic steps for its complete de novo construction. Surprisingly, the nutrient is synthesised by one of two related, though genetically distinct, pathways that represent aerobic or anaerobic routes. The anaerobic pathway has remained poorly characterised due to the instability of the pathway intermediates to oxygen and the low activity of enzymes, and is the focus of the research reported in this thesis. The Gram-positive aerobe Bacillus megaterium has previously been used for the commercial production of cobalamin and has a complete anaerobic pathway. Several genes, (termed chi for cobinamide biosynthesis) from the cobalamin biosynthetic pathway have been cloned and overexpressed individually within the host B. megaterium DSM319. One of the major bottlenecks in the anaerobic pathway is the ring contraction step, where only limited yields (

HPC clusters have become ever more expensive, both in terms of capital cost and energy consumption - some estimates suggest that competitive installations at the end of the next decade will require their own power station. One way around this looming problem is to design bespoke computing engines, but while the performance benefits are good, the design costs are huge and cannot easily be amortized. POETS (Partially Ordered Event Triggered System) - the focus of this paper - seeks to exploit a middle way: the architecture is tuned to a specific algorithmic pattern, but within that constraint, is fully programmable. POETS software is quasi-imperative: the user defines a set of sequential event handlers, defines the topology of a (typically large) concurrent ensemble of these, and lets them interact. The 'solution' may be exfiltrated from the emergent behaviour of the ensemble. In this paper, we describe (briefly) the architecture, and an example computational chemistry application, dissipative particle dynamics (DPD). The DPD algorithm is traditionally implemented using parallel computational techniques, but we re-cast it as a concurrent compute problem which is then ideally suited to POETS. Our prototype system is realised on a cluster of 48 FPGAs providing 50K concurrent hardware threads, and we report performance speedups of over two orders of magnitude better than a single thread baseline comparator, and scaling behaviour that is almost constant. The results are validated against a "conventional" implementation.

The EN-HE group operates more than 350 overhead travelling cranes, requiring a regular maintenance de-fined by CERN Safety Rules (GSI-M-1). An analysis made in 2020 concluded that important savings on preven-tive maintenance could be done by changing the actual strategy based on a fixed periodicity to a strategy based on the usage of each crane. To be able to implement such change, the usage of each crane has to be known and remotely communicated on a daily basis. This prerequisite is being fulfilled thanks to an economic solution based on IoT devices connected to each crane and relying on new LoRa network in surface and the LTE (GSM) network in underground locations. This presentation focuses on the initial context including the financial stakes, the deployed solution based on IoT devices, the challenges, the results obtained and the possible perspectives for a wider usage at CERN.

Existing high-end embedded systems face frequent security attacks. Software compartmentalization is one technique to limit the attacks' effects to the compromised compartment and not the entire system. Unfortunately, the existing state-of-the-art embedded hardware-software solutions do not work well to enforce software compartmentalization for high-end embedded systems. MPUs are not fine-grained and suffer from significant scalability limitations as they can only protect a small and fixed number of memory regions. On the other hand, MMUs suffer from non-determinism and coarse-grained protection. This paper introduces CompartOS as a lightweight linkage-based compartmentalization model for high-end, complex, mainstream embedded systems. CompartOS builds on CHERI, a capability-based hardware architecture, to meet scalability, availability, compatibility, and fine-grained security goals. Microbenchmarks show that CompartOS' protection-domain crossing is 95% faster than MPU-based IPC. We applied the CompartOS model, with low effort, to complex existing systems, including TCP servers and a safety-critical automotive demo. CompartOS not only catches 10 out of 13 FreeRTOS-TCP published vulnerabilities that MPU-based protection (e.g., uVisor) cannot catch but can also recover from them. Further, our TCP throughput evaluations show that our CompartOS prototype is 52% faster than relevant MPU-based compartmentalization models (e.g., ACES), with a 15% overhead compared to an unprotected system. This comes at an FPGA's LUTs overhead of 10.4% to support CHERI for an unprotected baseline RISC-V processor, compared to 7.6% to support MPU, while CHERI only incurs 1.3% of the registers area overhead compared to 2% for MPU.

The Gatsby Good Practical Science report (Gatsby, 2017) identified opportunities to carry out open-ended investigative projects as one of ten benchmarks for good practical science. However, there is currently no requirement for post-16 students in England to have access to such opportunities as this is not required by A-level specifications (the most common post-16 qualification in England). Nevertheless, some teachers incorporate open-ended investigative work into post-16 teaching. Drawing on in-depth semi-structured interviews with 12 teachers, enablers of and barriers to open-ended investigation are identified, and the ways in which several teachers have successfully implemented such work are demonstrated through vignettes. Ways that teachers can use and value open-ended project work within current A-level specifications are presented.

Additional file 1. Additional figures and tables.

Additional file 2. Extracted ion chromatograms and example LC-MS calibration data.

Barrier primitives provided by standard parallel programming APIs are the primary means by which applications implement global synchronisation. Typically these primitives are fully-committed to synchronisation in the sense that, once a barrier is entered, synchronisation is the only way out. For message-passing applications, this raises the question of what happens when a message arrives at a thread that already resides in a barrier. Without a satisfactory answer, barriers do not interact with message-passing in any useful way. In this paper, we propose a new refutable barrier primitive that combines with message-passing to form a simple, expressive, efficient, well-defined API. It has a clear semantics based on termination detection, and supports the development of both globally-synchronous and asynchronous parallel applications. To evaluate the new primitive, we implement it in a prototype large-scale message-passing machine with 49,152 RISC-V threads distributed over 48 FPGAs. We show that hardware support for the primitive leads to a highly-efficient implementation, capable of synchronisation rates that are an order-of-magnitude higher than what is achievable in software. Using the primitive, we implement synchronous and asynchronous versions of a range of applications, observing that each version can have significant advantages over the other, depending on the application. Therefore, a barrier primitive supporting both styles can greatly assist the development of parallel programs.

Caffeinated energy drink (ED) consumption has grown rapidly worldwide, particularly among young people. This review considers whether the health outcomes associated with young people’s energy drink consumption are too narrowly focused on physiological mechanisms, and whether there is evidence to support the hypothesis that energy drink consumption incurs broader social costs. A narrative review of studies published between 1997 and 2017 was undertaken. The focus was the behavioural, physical and mental health outcomes associated with sugar (including glucose, sucrose and fructose) and caffeine, the two main ingredients of EDs. Possible causal mechanisms linking ingredient to outcome are discussed. The population of interest was children and adolescents aged 6 to 18 years of age. A total of 33 studies were identified. ED consumption was found to be associated with health problems including high blood pressure, cardiovascular disease, headaches, sleep disorder, substance use, stress and hyperactivity however causal relationships could not be determined for all outcomes. The caffeine and sugar contained in EDs can promote adverse effects on children and adolescents. There is a weak evidence that these effects could extend beyond physical health to educational attainment, mental health and substance use. Increased awareness and further prospective studies are required.

Commodity FPGA boards with advanced networking facilities have great potential in the construction of high-performance compute clusters that scale. However, low-level design tools and long synthesis times are major barriers to productivity for application developers. In this paper, we explore the potential of a distributed soft-processor overlay, programmed in software at a high-level of abstraction, to deliver a useful level of performance for FPGA clusters. In particular, we demonstrate the use of hardware multhreading to achieve a fast, space-efficient, high-throughput overlay, and compare a 12-FPGA instance of it (12,288 RISC-V threads) against a conventional Xeon cluster on the problem of distributed graph processing.

Background: The World Health Organization recommends early breastfeeding initiation, within the first hour of life. Ugandan mothers with no formal schooling appear superior in fulfilling this recommendation compared to mothers with primary, secondary, or higher education. Aim: This secondary analysis of Ugandan Demographic and Health Survey data from 2016 aimed to statistically analyze the association between maternal education and early breastfeeding initiation, to find socio-economic and health care determinants that promote the behavior. Methods: Ugandan mothers (n=9,209, 15 to 49 years) were included in statistical analysis. Chi-squared testing and logistic regression were used to assess associations between maternal education (exposure) and fulfillment of early breastfeeding initiation less than 1 hour after birth (outcome). Results: Out of the eligible mothers in a weighted sample, 68% (n=6,281) fulfilled early breastfeeding initiation and 32% (n=2,928) did not meet the criteria. Maternal primary education significantly predicted the outcome of early breastfeeding initiation (p ≤ 0.05, AOR: 0.80, with 95% CI 0.67-0.95) in a negative direction, compared to uneducated mothers. This result was adjusted for maternal residence, education, occupation, and parity, along with the husband/partner's education. Moreover, educational attainment beyond the primary level indicated a non-significant association to the criteria fulfillment when compared to uneducated mothers. Conclusions: Ugandan maternal education does not seem to significantly promote early BFI behavior. Primary level education only indicated a significantly negative association compared to uneducated Ugandan mothers. Traditional lifestyle factors (lower level education, and corresponding level of occupation, and larger families) appeared to be associated with the desired behavior.

Direct Memory Access (DMA) attacks have been known for many years: DMA-enabled I/O peripherals have complete access to the state of a computer and can fully compromise it including reading and writing all of system memory. With the popularity of Thunderbolt 3 over USB Type-C and smart internal devices, opportunities for these attacks to be performed casually with only seconds of physical access to a computer have greatly broadened. In response, commodity hardware and operating-system (OS) vendors have incorporated support for Input-Output Memory Management Units (IOMMUs), which impose memory protection on DMA, and are widely believed to protect against DMA attacks. We investigate the state-of-the-art in IOMMU protection across OSes using a novel I/O security research platform, and find that current protections fall short when faced with a functional network peripheral that uses its complex interactions with the OS for ill intent, and demonstrate compromises against macOS, FreeBSD, and Linux, which notionally utilize IOMMUs to protect against DMA attackers. Windows only uses the IOMMU in limited cases and remains vulnerable. Using Thunderclap, an open-source FPGA research platform we built, we explore a number of novel exploit techniques to expose new classes of OS vulnerability. The complex vulnerability space for IOMMU-exposed shared memory available to DMA-enabled peripherals allows attackers to extract private data (sniffing cleartext VPN traffic) and hijack kernel control flow (launching a root shell) in seconds using devices such as USB-C projectors or power adapters. We have worked closely with OS vendors to remedy these vulnerability classes, and they have now shipped substantial feature improvements and mitigations as a result of our work.

Executive Summary • Serious violence levels and trends in England and Wales were studied based on data from a structured sample of 94 Emergency Departments (EDs), Minor Injury Units (MIUs) and Walk-in Centres. All are certified members of the National Violence Surveillance Network (NVSN). • Overall, an estimated 190,747 people attended EDs in England and Wales for treatment following violence in 2017, 1942 more than in 2016; a 1% increase. Falls or no change in overall violence levels in England and Wales according to this public health measure over the past decade were maintained in 2017. • In 2017, males (4.6 per 1,000 residents) were more than twice as likely as females (1.9 per 1,000 residents) to be treated in EDs following injury in violence. • Increases in violent injury among those aged 0-10 years (11%), 31-50 years (4.6%) and those aged 51 years and over (2.1%) were offset by the 1.8% decrease in violence among those aged 18-30 years. Due to small numbers, NVSN is unable to provide reliable violence trends for those aged 0-10 years. • Implementation of the new Emergency Care Data Set (ECDS) in Type 1 EDs in England led to increases in violence recording in the three months, October to December 2017. • Those most at risk of violence-related injury were males and those aged 18 to 30. Violence-related ED attendance was most frequent on Saturdays and Sundays.

Premises licensed for the sale and consumption of alcohol can contribute to levels of assault-related injury through poor operational practices that, if addressed, could reduce violence. We tested the real-world effectiveness of an intervention designed to change premises operation, whether any intervention effect changed over time, and the effect of intervention dose. A parallel randomized controlled trial with the unit of allocation and outcomes measured at the level of individual premises. All premises (public houses, nightclubs or hotels with a public bar) in Wales, UK. A randomly selected subsample (n = 600) of eligible premises (that had one or more violent incidents recorded in police-recorded crime data; n = 837) were randomized into control and intervention groups. Intervention premises were audited by Environmental Health Practitioners who identified risks for violence and provided feedback by varying dose (informal, through written advice, follow-up visits) on how risks could be addressed. Control premises received usual practice. Police data were used to derive a binary variable describing whether, on each day premises were open, one or more violent incidents were evident over a 455-day period following randomization. Due to premises being unavailable at the time of intervention delivery 208 received the intervention and 245 were subject to usual practice in an intention-to-treat analysis. The intervention was associated with an increase in police recorded violence compared to normal practice (hazard ratio = 1.34, 95% confidence interval = 1.20-1.51). Exploratory analyses suggested that reduced violence was associated with greater intervention dose (follow-up visits). An Environmental Health Practitioner-led intervention in premises licensed for the sale and on-site consumption of alcohol resulted in an increase in police recorded violence. UKCRC Public Health Research Centre of Excellence. Grant Number: MR/KO232331/1. National Institute of Health Research Public Health Research (NIHR PHR) Programme. Grant Number: 10/3010/21

Background and Aims: \ud \ud Premises licensed for the sale and consumption of alcohol can contribute to levels of assault-related injury through poor operational practices that, if addressed, could reduce violence. We tested the real-world effectiveness of an intervention designed to change premises operation, whether any intervention effect changed over time, the effect of intervention dose and cost effectiveness of the intervention.\ud Design: \ud \ud A parallel randomised controlled trial with the unit of allocation and outcomes measured at the level of individual premises.\ud Setting: \ud \ud All premises (public houses, night clubs, or hotels with a public bar) in Wales, UK.\ud Participants: \ud \ud A randomly selected subsample (N = 600) of eligible premises (that had one or more violent incidents recorded in police recorded crime data; N = 837) were randomised into control and intervention groups.\ud Intervention and Comparator: \ud \ud Intervention premises were audited by Environmental Health Practitioners who identified risks for violence and provided feedback by varying dose (informal, through written advice, follow-up visits) on how risks could be addressed. Control premises received usual practice.\ud Measurements: \ud \ud Police data were used to derive a binary variable describing whether, on each day premises were open, one or more incidents were evident over a 455 day period following randomisation.\ud Findings: \ud \ud Due to premises being unavailable at the time of intervention delivery 208 received the intervention and 245 were subject to usual practice in an intention to treat analysis. The intervention was associated with an increase in violence compared to normal practice (HR = 1.34, 95% CI 1.20 to 1.51). Exploratory analyses suggested that reduced violence was associated with greater intervention dose (follow-up visits).\ud Conclusion: \ud \ud An Environmental Health Practitioner led intervention in premises licensed for the sale and on-site consumption of alcohol resulted in an increase in police recorded violence.

Objectives:\ud The ELAStiC (Electronic Longitudinal Alcohol Study in Communities) project was established to determine factors that predict pathways into alcohol misuse and the life-course effects of alcohol use and misuse on health and well-being. This is achieved through accessing existing longitudinal data that are key sources of evidence for social and health policy, developing statistical methods and modelling techniques from a diverse range of disciplines, working with stakeholders in both policy, practice and the third sector to bring relevance to the work, and to bring together a diverse team of experts to collaborate and facilitate learning across diverse fields.\ud \ud Approach:\ud The project will link data that include cohort studies such as; UK Biobank, ALSPAC (Avon Longitudinal Study of Parents and Children), Millennium Cohort Study, British Household Panel Survey, Understanding Society, E_CATALyST (Caerphilly Health and Social Needs Electronic Cohort Study) and WECC (Wales Electronic Cohort for Children). These data will be linked with routine data from primary and secondary healthcare in England, Scotland and Wales. Additional data from education and police data source will also be linked as part of the project.\ud \ud The main work packages for the project are:\ud \ud Methodological Innovations:\ud Methodological developments in mechanisms for correcting bias in reporting alcohol consumption and for combining routine data with cohort data; the application of Markov models for examining the extent to which past behaviour influences future behaviour, and econometric hedonic pricing methods for providing insights into the costs of alcohol-related harm.\ud \ud Pathways into Harm:\ud Do family structure, household composition, youngsters’ previous ill-health and educational attainment predict their use of alcohol and what socio-economic factors and household transitions contribute to hazardous alcohol consumption in adults?\ud \ud Secondary Harms:\ud What is the effect on children’s health and educational achievement of living in households in which one or more adults has experienced alcohol-related harm?\ud \ud Mental Health & Well-Being:\ud What is the relationship between alcohol consumption, hospital admission and mental health in adults and children?\ud \ud Results:\ud The results of the data linkage between the multiple cohorts and health, education and police data will be reported. The challenges of linking cohort and other data types from different nations will be discussed.\ud \ud Conclusions:\ud Our project will aim to provide evidence that informs the UK Government’s commitment to “radically reshape the approach to alcohol and reduce the number of people drinking to excess”, by working with existing longitudinal data collected in the UK to inform policy and practice.

Cell-free transcription – translation is an expanding fi eld in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identi fi ca- tion of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells.

Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilization of methane through anaerobic methane oxidation. The enzyme uses an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a methyl radical/Ni(II)-thiolate intermediate. However, it is unclear how coenzyme F430 is synthesized from the common primogenitor uroporphyrinogen III, incorporating 11 steric centres into the macrocycle, although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamization and carbocyclic ring formation. Here we identify the proteins that catalyse the biosynthesis of coenzyme F430 from sirohydrochlorin, termed CfbA–CfbE, and demonstrate their activity. The research completes our understanding of how the repertoire of tetrapyrrole-based pigments are constructed, permitting the development of recombinant systems to use these metalloprosthetic groups more widely.

Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilization of methane through anaerobic methane oxidation. The enzyme uses an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a methyl radical/Ni(ii)-thiolate intermediate. However, it is unclear how coenzyme F430 is synthesized from the common primogenitor uroporphyrinogen iii, incorporating 11 steric centres into the macrocycle, although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamization and carbocyclic ring formation. Here we identify the proteins that catalyse the biosynthesis of coenzyme F430 from sirohydrochlorin, termed CfbA-CfbE, and demonstrate their activity. The research completes our understanding of how the repertoire of tetrapyrrole-based pigments are constructed, permitting the development of recombinant systems to use these metalloprosthetic groups more widely.

Streptomyces venezuelae is a promising chassis in synthetic biology for fine chemical and secondary metabolite pathway engineering. The potential of S. venezuelae could be further realized by expanding its capability with the introduction of its own in vitro transcription-translation (TX-TL) system. TX-TL is a fast and expanding technology for bottom-up design of complex gene expression tools, biosensors and protein manufacturing. Herein, we introduce a S. venezuelae TX-TL platform by reporting a streamlined protocol for cell-extract preparation, demonstrating high-yield synthesis of a codon-optimized sfGFP reporter and the prototyping of a synthetic tetracycline-inducible promoter in S. venezuelae TX-TL based on the tetO-TetR repressor system. The aim of this system is to provide a host for the homologous production of exotic enzymes from Actinobacteria secondary metabolism in vitro. As an example, the authors demonstrate the soluble synthesis of a selection of enzymes (12-70 kDa) from the Streptomyces rimosus oxytetracycline pathway.

Background: Rugby Union is a popular contact sport played worldwide. The physical demands of the game are characterized by short duration, high intensity bouts of activity, with collisions between players, often while running fast. The head, neck, upper limb and lower limb are common sites for injury. Although catastrophic injuries are rare in rugby, they do occur. Immediate action (4-hour window) must occur after the injury to minimise the damage incurred from a catastrophic injury. This infers that a well-functioning medical infrastructure should be available to anticipate injuries of this nature and provide treatment for the best possible outcome. Currently there is no system information/map in South Africa describing the medical infrastructure in relation to places where clubs and schools practice and play matches. Such a system may assist providing early and immediate transfer of injured players to the appropriate treatment facility. This would minimise the damaging effects caused by delays in medical treatment. Therefore the aim of this study was to; (i) investigate and report on the location, distance and travel time from rugby playing/training venues in the Eastern Cape to the nearest specialist hospital where a player may be able to receive adequate treatment for a catastrophic injury, and ii) report on safety equipment available at these playing venues to facilitate this transport in a safe manner. Methods: All the clubs (n=403) and schools (n =264) that played rugby in the Eastern Cape were accounted for in the study. However, only 15 clubs and 35 schools were included in the analysis as they had their own facilities for training and playing matches. Distances between clubs/schools and the nearest public, private and specialized hospital (able to treat catastrophic injuries) were measured. In addition driving time was also estimated between the clubs/schools and nearest specialized hospital to determine if an injured player could be transported within four hours to receive medical treatment for a catastrophic injury. In addition medical safety equipment was audited (according to information provided by SA RUGBY)) for each club and school to identify if they were meeting the minimum safety standards as set by SA RUGBY. Results: Twenty schools were identified as being less than one hour away from the nearest hospital equipped to deal with catastrophic rugby injuries; nine schools were between 1-2 hours away and six schools were between 2-3 hours away. All schools were within 100 km driving distance of the nearest public hospital; 28 schools were within 100km driving distance to the nearest private hospital. For seven schools, the nearest private hospital was between 100 and 150 km away. Fourteen schools had spinal boards, eleven had neck braces, ten had harnesses, nine had change rooms, five had floodlights, and twenty-two had trained first aiders. Six schools were located 2-3 hours away and were at higher risk due to a lack of first aid equipment. Ten clubs were less than an hour away from the nearest hospital equipped to treat catastrophic injuries; two clubs were between 1-2 hours away, two were between 2-3 hours away and one was between 3-4 hours away. All clubs were within 100 km driving distance of the nearest public hospital. Nine clubs were within 100km driving distance to the nearest private hospital, three clubs were based between 100 and 150 km from the nearest private hospital and three were based over 150km away from the nearest private hospital. Twelve clubs had a spinal board, eleven clubs had neck braces, ten clubs had harnesses, ten clubs had change rooms, seven clubs had floodlights and twelve clubs had first aid trainers. One club was classified as high risk as it was located 2-3 hours away from the nearest hospital equipped to manage a catastrophic injury and had no first aid equipment. Discussion/Conclusion: No clubs or schools included in the study were more than four hours away from a hospital that was equipped to deal with a catastrophic rugby injury. Therefore, any player who suffers a catastrophic injury should be able to get to treatment within the 4-hour window period. Another finding was that not all clubs or schools possessed the minimum equipment required to host training or a rugby match. SA RUGBY can take appropriate action towards these clubs and schools to ensure that they maintain the safest possible practice to not put their own players at increased risk.

Participation in organised activities (OAs) such as sports and special groups can shape adolescent risk taking behaviours. Sensation seeking and inhibitory control play an important role in the emergence of adolescent risk taking behaviours and may explain variations in OA participation as well as inform the development of more effective interventions that use OAs. Data from the Avon Longitudinal Study of Parents and Children (England) were analysed using logistic regression to test whether inhibitory control and sensation seeking predicted participation in OAs at a mean age of 11.7 years (n = 2557) and 15.4 years (n = 2147). At 11 years of age higher sensation seeking predicted participation in any activity, sports and special groups while low inhibitory control predicted less participation in sports. At 15 years of age higher sensation seeking predicted participation in sports and activity breadth. Opportunities to develop targeted interventions aimed at increasing participation are discussed.

Golden Gate cloning is a prominent DNA assembly tool in synthetic biology for the assembly of plasmid constructs often used in combinatorial pathway optimisation, with a number of assembly kits developed specifically for yeast and plant-based expression. However, its use for synthetic biology in commonly used bacterial systems such as Escherichia coli, has surprisingly been overlooked. Here, we introduce EcoFlex a simplified modular package of DNA parts for a variety of applications in E. coli, cell-free protein synthesis, protein purification and hierarchical assembly of transcription units based on the MoClo assembly standard. The kit features a library of constitutive promoters, T7 expression, RBS strength variants, synthetic terminators, protein purification tags and fluorescence proteins. We validate EcoFlex by assembling a 68-part containing (20 genes) plasmid (31 kb), characterise in vivo and in vitro library parts, and perform combinatorial pathway assembly, using pooled libraries of either fluorescent proteins or the biosynthetic genes for the antimicrobial pigment violacein as a proof-of-concept. To minimise pathway screening, we also introduce a secondary module design site to simplify MoClo pathway optimisation. In summary, EcoFlex provides a standardised and multifunctional kit for a variety of applications in E. coli synthetic biology.

Supplemental material, Supplementary_material_1 for I am going to make the most out of it! Italian university Credit Mobility Students’ social representations of alcohol use during study abroad experiences by Giovanni Aresi, Francesco Fattori, Maura Pozzi and Simon C Moore in Journal of Health Psychology

In this paper, we explore the designs of a circuit-switched router, a wormhole router, a quality-of-service (QoS) supporting virtual channel router and a speculative virtual channel router and accurately evaluate the energy-performance tradeoffs they offer. Power results from the designs placed and routed in a 90-nm CMOS process show that all the architectures dissipate significant idle state power. The additional energy required to route a packet through the router is then shown to be dominated by the data path. This leads to the key result that, if this trend continues, the use of more elaborate control can be justified and will not be immediately limited by the energy budget. A performance analysis also shows that dynamic resource allocation leads to the lowest network latencies, while static allocation may be used to meet QoS goals. Combining the power and performance figures then allows an energy-latency product to be calculated to judge the efficiency of each of the networks. The speculative virtual channel router was shown to have a very similar efficiency to the wormhole router, while providing a better performance, supporting its use for general purpose designs. Finally, area metrics are also presented to allow a comparison of implementation costs.

Background\ud \ud Children with antisocial behaviour show deficits in the perception of emotional expressions in others that may contribute to the development and persistence of antisocial and aggressive behaviour. Current treatments for antisocial youngsters are limited in effectiveness. It has been argued that more attention should be devoted to interventions that target neuropsychological correlates of antisocial behaviour. This study examined the effect of emotion recognition training on criminal behaviour.\ud \ud Methods\ud \ud Emotion recognition and crime levels were studied in 50 juvenile offenders. Whilst all young offenders received their statutory interventions as the study was conducted, a subgroup of twenty-four offenders also took part in a facial affect training aimed at improving emotion recognition. Offenders in the training and control groups were matched for age, SES, IQ and lifetime crime level. All offenders were tested twice for emotion recognition performance, and recent crime data were collected after the testing had been completed.\ud \ud Results\ud \ud Before the training there were no differences between the groups in emotion recognition, with both groups displaying poor fear, sadness and anger recognition. After the training fear, sadness and anger recognition improved significantly in juvenile offenders in the training group. Although crime rates dropped in all offenders in the 6 months following emotion testing, only the group of offenders who had received the emotion training showed a significant reduction in the severity of the crimes they committed.\ud \ud Conclusions\ud \ud The study indicates that emotion recognition can be relatively easily improved in youths who engage in serious antisocial and criminal behavior. The results suggest that improved emotion recognition has the potential to reduce the severity of reoffending.

Aims:\ud The purpose of this research was to test and compare associations between participation in organised activities and indicators of hazardous drinking between young offenders and young non-offenders.\ud Methods:\ud Two groups of 13–18 year-old males were recruited in Cardiff, UK: 93 young offenders and 53 non-offenders from secondary schools matched on estimated IQ, sex and socioeconomic status. Indicators of hazardous drinking were measured using the Fast Alcohol Screening Test (FAST). Organised activity participation and externalising behaviour was measured by the Youth Self Report. The Wechsler Abbreviated Scale of Intelligence was also administered.\ud Results:\ud Young offenders participated in fewer organised activities and had higher FAST scores than non-offenders. Young offenders and non-offenders significantly differed on mean FAST scores if they participated in no organised activities but not if they participated in at least one team sport. Externalising behaviour problems were unrelated to participation in organised activities.\ud Conclusions:\ud Although young offenders were less likely to have participated in organised activities, for them, participation in a team sport was associated with less hazardous drinking. Vulnerable youths who might benefit most from sporting activities actually access them the least. Future research should identify the different barriers to participation that they face.

While there has been much research investigating the\ud consequences of viewing media violence, there is comparatively little research on the antecedents of viewing it. Television relies primarily on visual imagery but as yet there has been little research concernIng viewers' visual Imagery ability. It is hypothesized that viewers with vivid visual imagery have, in contrast to non-vivid visual imagers, the skills necessary to manipulate violent images of real events and distance themselves from them. Thus it was predicted that non-vivid visual imagers would show more elevated physiological and emotional responses to real violence. If physiology is a substrate of aggression then features that have been seen to change levels of behavioural aggression in previous studies should have similar effects on physiology. Previous research has suggested that it is real rather than fictional violence that has the greatest effect on viewers\ud (Berkowitz & Alioto, 1973; Geen, 1975). It has also been\ud suggested that increases in physiological activity can have an\ud intensifying effect on emotional states, giving it "visceral quality" (Schacter & Singer, 1962; Reisenzein, 1983). Thus it was predicted that real violence would produce the greatest increases In both physiology and negative mood experience. In a series of four experiments 140 participants' heart rates, electrodermal activity and mood states were assessed in response to differing types of film violence. As predicted, participants' physiological responses, particularly heart rates, were more elevated to real violence, an effect that was reflected in negative mood ratings. Variables such as violence-justification and the type of violence were also seen to yield differential physiological activity. There was also evidence, as predicted, that non-vivid imagers were more physiologically reactive to real violence than high imagers, although this was not reflected in mood rating differences. These results suggest that physiological responses are a fundamental component of aggression and that they play an important role in determining the level of emotional experience. Individual difference factors such as visual imagery ability also play an influential role In shaping responses to media violence.

Tyrosine phosphorylation of the substrate domain of Cas (CasSD) correlates with increased cell migration in healthy and diseased cells. Here, we address the mechanism leading to the phosphorylation of CasSD in the context of fibronectin-induced early spreading of fibroblasts. We have previously demonstrated that mechanical stretching of CasSD exposes phosphorylation sites for Src family kinases (SFKs). Surprisingly, phosphorylation of CasSD was independent of myosin contractile activity but dependent on actin polymerization. Furthermore, we found that CasSD phosphorylation in the early stages of cell spreading required: (1) integrin anchorage and integrin-mediated activation of SFKs, (2) association of Cas with focal adhesion kinase (FAK), and (3) N-WASP-driven actin-assembly activity. These findings, and analyses of the interactions of the Cas domains, indicate that the N-terminus of Cas associates with the FAK-N-WASP complex at the protrusive edge of the cell and that the C-terminus of Cas associates with the immobilized integrin-SFK cluster. Thus, extension of the leading edge mediated by actin polymerization could stretch Cas during early cell spreading, priming it for phosphorylation.

This paper presents a cache tracker, a hardware component to track the cache state of hundreds of caches serving processors modeled using threads on a single MIPS64 processor. This host-multithreading approach allows a single, low-cost FPGA to model large systems to allow quick and broad architectural exploration with reasonable simulation performance. The cache tracker stores all state in DRAM to allow maximum scalability in both number of processors and in cache sizes. We describe our approach of scalability versus simulation performance, our implementation in Bluespec SystemVerilog, and give a sample study of a parallel merge-sort over various processor numbers, cache sizes and arrangements.

Rational offender models assume that individuals choose whether to offend by weighing the rewards against the chances of apprehension and the penalty if caught. While evidence indicates that rational theory is applicable to acquisitive crimes, the explanatory power for gratuitous non-fatal violent offending has not been evaluated. Lottery-type questions elicited risk attitudes and time preferences from respondents in a street survey. Admitted violent behaviour was predictable on the basis of some of these responses. Consistent with the rational model, less risk averse and more impatient individuals were more liable to violence. Such people were also more likely to be victims of violence. In line with a ‘subjective’ version of the rational model, respondents with lower estimates of average violence conviction chances and of fines were more prone to be violent.

Rational offender models assume that individuals choose whether to offend by weighing the rewards against the chances of apprehension and the penalty if caught. While evidence indicates that rational theory is applicable to acquisitive crimes, the explanatory power for gratuitous non-fatal violent offending has not been evaluated. Lottery-type questions elicited risk attitudes and time preferences from respondents in a street survey. Admitted violent behaviour was predictable on the basis of some of these responses. Consistent with the rational model, less risk averse and more impatient individuals were more liable to violence. Such people were also more likely to be victims of violence. In line with a subjective version of the rational model, respondents with lower estimates of average violence conviction chances and of fines were more prone to be violent.

Aims: First, to assess whether perpetrators of violence are also more likely to be victims of violence in a sample of drinkers who socialize in a city centre night-time economy. Second, to test whether extent of alcohol use and impulsive decision making, both associated with violence and violent injury, are associated with violence and victimization equally.\ud \ud Design: A cross-sectional street survey conducted in an area characterized by a high density of licensed premises collected data on socio-economic status, gender, alcohol consumption, impulsive decision making and whether respondents had been victims of violence or had perpetrated violence. Impulsive decision making was assessed using a delay discounting task with hypothetical monetary rewards.\ud \ud Participants: Data from 271 female and 294 male respondents who regularly socialized in the local night time economy were available for analysis.\ud \ud Findings: Perpetrators of violence were more likely to be victims of violence; impulsive decision making predicted violence whereas alcohol consumption and the frequency that respondents visited the night time economy predicted victimization. Men were more likely to be perpetrators of violence than women.\ud \ud \ud Conclusions: Heavy alcohol consumption in areas densely populated with licensed premises increases the likelihood of victimization and perpetrators of violence are more likely to disregard the future consequences of their action. Measures that either reduce the impact of drunken behavior or reduce excessive alcohol consumption will reduce alcohol related harm.

We describe a method for standardizing cytotoxicity assays by the use of cryopreserved, fluorescently labeled target cells. The cells are labeled in batches with the fluorogenic element europium (Eu) and frozen in multiple aliquots. Replicate aliquots can be thawed on different days and used for cytotoxicity assays. Thawed pre-labeled cells from the same batch are killed reproducibly, allowing cytotoxicity assays to be standardized. The target cells need only be thawed, washed, counted for viability and used. The availability of pre-labeled, cryopreserved targets facilitates the assessment of cytotoxic activity of individual donors at different times. The method also simplifies the use of large panels of target cell types. By using this procedure it is not necessary to maintain active cultures of target cells, nor is it necessary to use and dispose of radioisotopes. These pre-labeled target cells can be used in various assays where the result is a destroyed target cell such as cell-mediated cytotoxicity, complement mediated cytotoxicity, or antibody-dependent cellular cytotoxicity.

Until now, most cryptography implementations on parallel architectures have focused on adapting the software to SIMD architectures initially meant for media applications. In this paper, we review some of the most significant contributions in this area. We then propose a vector architecture to efficiently implement long precision modular multiplications. Having such a data level parallel hardware provides a circuit whose decode and schedule units are at least of the same complexity as those of a scalar processor. The excess transistors are mainly found in the data path. Moreover, the vector approach gives a very modular architecture where resources can be easily redefined. We built a functional simulator onto which we performed a quantitative analysis to study how the resizing of those resources affects the performance of the modular multiplication operation. Hence we not only propose a vector architecture for our Public Key cryptographic operations but also show how we can analyze the impact of design choices on performance. The proposed architecture is also flexible in the sense that the software running on it would offer room for the implementation of counter-measures against side-channel or fault attacks.

This study investigates the selective formation of higher oxygenates from a synthesis gas mixture using a variety of copper-based heterogeneous catalysts. The catalysts are prepared by co-precipitation. Full characterisation of the catalysts, both before and after use, is achieved using primarily by spectroscopy, thermogravimetric and X-ray analysis and BET and copper surface area measurements. The catalytic activities and selectivities of the products are determined from the reaction of synthesis gas mixtures (H2/CO/CO2) in a self-built continuous flow microreactor, equipped with on-line gas chromatographic analysis, operating at moderate temperature and pressure. The activity is measured in terms of conversion from reactants and the conversion and product distribution of all products formed determine the selectivity of higher alcohols. These factors can be determined by variation in the reactor gasfeed composition, the pressure, the temperature and the gas hourly space velocity. The effect on selectivity of production by the addition of lower alcohol (methanol or ethanol) to the reactant mixture has also been examined. The variation in microreactor parameters can be related to possible correlations between catalyst structure and catalyst activity and selectivity. Preparation of the initial catalyst, Cu/Cr2O3, formed preferentially methanol; hydrocarbons and dimethyl ether were also produced. Substitution of chromium for aluminium and magnesium caused changes in product distribution; the aluminium for increasing activity and the magnesium to decrease the acidity. However, the initial preparation conditions for the Cu/MgO/Al2O3 (50/10/40) catalyst resulted in incomplete co-precipitation and a consequential decrease in activity such that no alcohols were produced. Methane was the primary product for this catalyst. Binary catalysts of Cu/MgO and Cu/Al2O3 were prepared to optimise the preparation condition to give complete co-precipitation. A main emphasis has been to establish preparation conditions, which have been shown to lead to reproducibility in catalyst structure and catalytic activity. The magnesium concentration was initially fixed at 2 % of the total metal content; however, this still resulted in the production of hydrocarbons and dimethyl ether. The magnesium concentration was gradually increased through 5 % to 7 % with respect to the copper and aluminium components. This increase in magnesium concentration resulted in a precursor with increased crystallinity and a catalyst, which gave a higher yield of higher alcohols. However, methanol was still the predominant alcohol in the total alcohol yield. At this increased magnesium concentration, hydrocarbons and dimethyl ether were still being produced. On the basis that the inhibiting step is the C1-C2 chain growth step, it has been found that this can be overcome by K-promotion of the Cu/Mg/Al203 (60/7/35) catalysts with the K+ ion at 0.005 wt %. This was especially noticeable with the catalyst prepared at pH = 8 and aged in the mother liquor for 30 mins, as a large production of ethanal was observed. Under the conditions used unlike unpromoted catalysts, no induction period in the formation of oxygenates was observed with these catalysts. However, the overall activity as measured by the consumption of the reactants was lower than that observed with unpromoted catalysts. No DME was formed with the K-promoted catalysts.

Participation in organised activities (OAs) such as sports and special groups can shape adolescent risk taking behaviours. Sensation seeking and inhibitory control play an important role in the emergence of adolescent risk taking behaviours and may explain variations in OA participation as well as inform the development of more effective interventions that use OAs. Data from the Avon Longitudinal Study of Parents and Children (England) were analysed using logistic regression to test whether inhibitory control and sensation seeking predicted participation in OAs at a mean age of 11.7 years (n = 2557) and 15.4 years (n = 2147). At 11 years of age higher sensation seeking predicted participation in any activity, sports and special groups while low inhibitory control predicted less participation in sports. At 15 years of age higher sensation seeking predicted participation in sports and activity breadth. Opportunities to develop targeted interventions aimed at increasing participation are discussed.