Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 beta-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogringreen fluorescent protein localization in the basal or secretagogue-stimulated state. By contrast, co-expression of Dyn/K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of beta-cell insulin secretion

Electromagnetic Induction Imaging of concealed metallic objects by means of resonating circuits

An electromagnetic induction system, suitable for 2D imaging of metallic samples of different electrical conductivities, has been developed. The system is based on a parallel LCR circuit comprising a ferrite-cored coil (7.8 mm x 9.5 mm, L=680 μH at 1 KHz), a variable resistor and capacitor. The working principle of the system is based on eddy current induction inside a metallic sample when this is introduced into the AC magnetic field created by the coil. The inductance of the LCR circuit is modified due to the presence of the sample, to an extent that depends on its conductivity. Such modification is known to increase when the system is operated at its resonant frequency. Characterizing different metals based on their values of conductivity is therefore possible by utilizing a suitable system operated at resonance. Both imaging and material characterization were demonstrated by means of the proposed electromagnetic induction technique. Furthermore, the choice of using a system with an adjustable resonant frequency made it possible to select resonances that allow magnetic-field penetration through conductive screens. Investigations on the possibility of imaging concealed metals by penetrating such shields have been carried out. A penetration depth of δ~3 mm through aluminium (Al) was achieved. This allowed concealed metallic samples- having conductivities ranging from 0.54 to 59.77 MSm-1 and hidden behind 1.5-mm-thick Al shields- to be imaged. Our results demonstrate that the presence of the concealed metallic objects can be revealed. The technique was thus shown to be a promising detection tool for security applications

Penetrating power of resonant electromagnetic induction imaging

The possibility of revealing the presence and identifying the nature of conductive targets is of central interest in many fields, including security, medicine, industry, archaeology and geophysics. In many applications, these targets are shielded by external materials and thus cannot be directly accessed. Hence, interrogation techniques are required that allow penetration through the shielding materials, in order for the target to be identified. Electromagnetic interrogation techniques represent a powerful solution to this challenge, as they enable penetration through conductive shields. In this work, we demonstrate the power of resonant electromagnetic induction imaging to penetrate through metallic shields (1.5-mm-thick) and image targets (having conductivities σσ ranging from 0.54 to 59.77 MSm−1m−1) concealed behind them

Magnetic imaging: a new tool for UK national nuclear security.

Combating illicit trafficking of Special Nuclear Material may require the ability to image through electromagnetic shields. This is the case when the trafficking involves cargo containers. Thus, suitable detection techniques are required to penetrate a ferromagnetic enclosure. The present study considers techniques that employ an electromagnetic based principle of detection. It is generally assumed that a ferromagnetic metallic enclosure will effectively act as a Faraday cage to electromagnetic radiation and therefore screen any form of interrogating electromagnetic radiation from penetrating, thus denying the detection of any eventual hidden material. In contrast, we demonstrate that it is actually possible to capture magnetic images of a conductive object through a set of metallic ferromagnetic enclosures. This validates electromagnetic interrogation techniques as a potential detection tool for National Nuclear Security applications

The role of affect regulation in the treatment of people who have committed sexual offences

Affect regulation problems have been found to play an important role in the onset of problematic behavior, such as sexual abuse. The role of emotion and maladaptive coping has become relevant in both research and treatment interventions. Forensic treatments have been strongly influenced by conceptualizations of affect regulation that emphasize the control of emotional experience and expression. For a long time, emotions were treated as less important than cognition. However, the view of emotion as an adaptive resource and meaning system is now emerging in the forensic literature. General psychotherapy research has shown that improved affect regulation and deeper experiencing is associated with better outcomes in psychotherapy. These findings, in combination with the role of emotions in behavioral and relational functioning, are leading to a shift in forensic treatment approaches. In this paper, we review the literature on affect regulation in treatment programs for individuals who have committed sexual offences. The implications of this work for forensic practice will be considered. Finally, Emotion-Focused Therapy will be presented as a promising therapeutic approach for forensic treatment programs to promote clients' emotional engagement and processing, and to improve treatment outcomes

Presence of Treponema denticola and Porphyromonas gingivalis in Children Correlated with Periodontal Disease of Their Parents

Considerable evidence exists suggesting that periodontal disease is due to the overgrowth of a finite number of specific bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Treponema denticola, Bacteroides forsythus, and Prevotella intermedia, among others. Three of these organisms-P. gingivalis, T. denticola, and B. forsythus—can be easily detected in plaque samples by the hydrolysis of the synthetic trypsin substrate benzoyl-DL-arginine-naphthylamide (BANA). The aim of the present study was to determine if a relationship could be found between the presence of either these organisms or periodontitis in the parent and the presence of BANA-positive species in the child. Thirty-four mothers or fathers and 34 children were examined for plaque scores, papillary bleeding scores, and the presence of P. gingivalis and T. denticola in four subgingival or marginal gingival plaque samples as assayed by the BANA test or specific polyclonal antibodies using an ELISA. Children whose parents were colonized by BANA-positive bacteria were 9.8 times more likely to be colonized by these BANA-positive species. Children whose parents had clinical evidence of periodontitis were 12 times more likely to be colonized by these BANA-positive species. These data are compatible with the hypothesis that children may acquire the BANA-positive species from their parents, especially if the parent has periodontitis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68201/2/10.1177_00220345940730100801.pd

Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.

INTRODUCTION: Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission. METHODS AND ANALYSIS: A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data. ETHICS AND DISSEMINATION: The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results]

Teaching, research or balanced? An exploration of the experiences of biomedical scientists working in UK medical schools

Driven by demand for high standards in university education, efforts have been made in the UK to address the perceived imbalance between teaching and research. However, teaching is still perceived by many as having less credibility and is attributed less importance. The purpose of our research was to explore how distinct types of academic job profiles (‘research’ or ‘education’ focused, or ‘balanced’) impact on biomedical scientists' perceptions of the lecturer role. Specifically, we investigated the experiences of biomedical scientists in ‘post-1990’ medical schools, which are known for their commitment to excellence in both research and education. We conducted 22 face-to-face, semi-structured interviews with biomedical scientists in five schools. Focusing on experiences of work, the interviews covered: ‘motivations’, ‘role expectations’, ‘teaching’, ‘research’ and ‘career’. The recorded qualitative data were transcribed and then analysed thematically. Our results, offering an insight into the working lives of biomedical scientists in medical education, suggest that in settings with a dual emphasis on education and research, individuals on ‘balanced’ contracts can experience a strong pull between research and teaching. In addition to posing significant challenges with respect to workload management, this can impact profoundly on professional identity. In contrast to the balanced role, ‘research’ or ‘education’ focused roles appear to have clearer requirements, leading to higher employee satisfaction. We conclude that to assist the educational mission of Higher Education, attention should be paid to balanced contracts, to (a) ensure employee support, (b) mitigate against negative perceptions of teaching, and ultimately, (c) guard against staff attrition

Hybridizing Constraint Programming and Monte-Carlo Tree Search: Application to the Job Shop problem

International audienceConstraint Programming (CP) solvers classically explore the solution space using tree search-based heuristics. Monte-Carlo Tree-Search (MCTS), a tree-search based method aimed at sequential decision making under uncertainty, simultaneously estimates the reward associated to the sub-trees, and gradually biases the exploration toward the most promising regions. This paper examines the tight combination of MCTS and CP on the job shop problem (JSP). The contribution is twofold. Firstly, a reward function compliant with the CP setting is proposed. Secondly, a biased MCTS node-selection rule based on this reward is proposed, that is suitable in a multiple-restarts context. Its integration within the Gecode constraint solver is shown to compete with JSP-specific CP approaches on difficult JSP instances

Ocean acidification boosts larval fish development but reduces the window of opportunity for successful settlement.

Author version of article published in final form at DOI: 10.1098/rspb.2015.1954© 2015 The Author(s) Published by the Royal Society. All rights reservedLocating appropriate settlement habitat is a crucial step in the life cycle of most benthic marine animals. In marine fish, this step involves the use of multiple senses, including audition, olfaction and vision. To date, most investigations of larval fish audition focus on the hearing thresholds to various frequencies of sounds without testing an ecological response to such sounds. Identifying responses to biologically relevant sounds at the development stage in which orientation is most relevant is fundamental. We tested for the existence of ontogenetic windows of reception to sounds that could act as orientation cues with a focus on vulnerability to alteration by human impacts. Here we show that larvae of a catadromous fish species (barramundi, Lates calcarifer) were attracted towards sounds from settlement habitat during a surprisingly short ontogenetic window of approximately 3 days. Yet, this auditory preference was reversed in larvae reared under end-of-century levels of elevated CO2, such that larvae are repelled from cues of settlement habitat. These future conditions also reduced the swimming speeds and heightened the anxiety levels of barramundi. Unexpectedly, an acceleration of development and onset of metamorphosis caused by elevated CO2 were not accompanied by the earlier onset of attraction towards habitat sounds. This mismatch between ontogenetic development and the timing of orientation behaviour may reduce the ability of larvae to locate habitat or lead to settlement in unsuitable habitats. The misinterpretation of key orientation cues can have implications for population replenishment, which are only exacerbated when ontogenetic development decouples from the specific behaviours required for location of settlement habitats.Australian Research Counci