511 research outputs found

    The role of surfactants in Köhler theory reconsidered

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    International audienceAtmospheric aerosol particles typically consist of inorganic salts and organic material. The inorganic compounds as well as their hygroscopic properties are well defined, but the effect of organic compounds on cloud droplet activation is still poorly characterized. The focus of the present study is the organic compounds that are surface active i.e. tend to concentrate on droplet surface and decrease the surface tension. Gibbsian surface thermodynamics was used to find out how partitioning between droplet surface and the bulk of the droplet affects the surface tension and the surfactant bulk concentration in droplets large enough to act as cloud condensation nuclei. Sodium dodecyl sulfate (SDS) was used together with sodium chloride to investigate the effect of surfactant partitioning on the Raoult effect (solute effect). While accounting for the surface to bulk partitioning is known to lead to lowered bulk surfactant concentration and thereby to increased surface tension compared to a case in which the partitioning is neglected, the present results show that the partitioning also alters the Raoult effect, and that the change is large enough to further increase the critical supersaturation and hence decrease cloud droplet activation. The fraction of surfactant partitioned to droplet surface increases with decreasing droplet size, which suggests that surfactants might enhance the activation of larger particles relatively more thus leading to less dense clouds. Cis-pinonic acid-ammonium sulfate aqueous solutions were studied in order to study the partitioning with compounds found in the atmosphere and to find out the combined effects of dissolution and partitioning behavior. The results show that the partitioning consideration presented in this paper alters the shape of the Köhler curve when compared to calculations in which the partitioning is neglected either completely or in the Raoult effect. In addition, critical supersaturation was measured for SDS particles with dry radii of 25-60nm using a static parallel plate Cloud Condensation Nucleus Counter. The experimentally determined critical supersaturations agree very well with theoretical calculations taking the surface to bulk partitioning fully into account and are much higher than those calculated neglecting the partitioning

    Health care professionals meeting with individuals with Type 2 diabetes and obesity: Balancing coaching and caution

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    The burden of diabetes and obesity is increasing worldwide, indicating a need to find the best standard for diabetes care. The aim of this study was to generate a theory grounded in empirical data derived from a deeper understanding of health care professionals’ main concerns when they consult with individuals with diabetes and obesity and how they handle these concerns. Tape-recorded interviews were conducted with seven groups and three individual members of a diabetes team in an area of western Sweden. The grounded theory (GT) method was used to analyse the transcribed interviews. A core category, labelled Balancing coaching and caution and three categories (Coaching and supporting, Ambivalence and uncertainty, and Adjusting intentions) emerged. The core category and the three categories formed a substantive theory that explained and illuminated how health care professionals manage their main concern; their ambition to give professional individualised care; and find the right strategy for each individual with diabetes and obesity. The theory generated by this study can improve our understanding of how a lack of workable strategies limits caregivers’ abilities to reach their goals. It also helps identify the factors that contribute to the complexity of meetings between caregivers and individuals with diabetes

    Basic Science in Movement Disorders: Fueling the Engine of Translation into Clinical Practice

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    \ua9 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Basic Science is crucial for the advancement of clinical care for Movement Disorders. Here, we provide brief updates on how basic science is important for understanding disease mechanisms, disease prevention, disease diagnosis, development of novel therapies and to establish the basis for personalized medicine. We conclude the viewpoint by a call to action to further improve interactions between clinician and basic scientists. \ua9 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

    Acute Stress Induces Contrasting Changes in AMPA Receptor Subunit Phosphorylation within the Prefrontal Cortex, Amygdala and Hippocampus

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    Exposure to stress causes differential neural modifications in various limbic regions, namely the prefrontal cortex, hippocampus and amygdala. We investigated whether α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) phosphorylation is involved with these stress effects. Using an acute inescapable stress protocol with rats, we found opposite effects on AMPA receptor phosphorylation in the medial prefrontal cortex (mPFC) and dorsal hippocampus (DH) compared to the amygdala and ventral hippocampus (VH). After stress, the phosphorylation of Ser831-GluA1 was markedly decreased in the mPFC and DH, whereas the phosphorylation of Ser845-GluA1 was increased in the amygdala and VH. Stress also modulated the GluA2 subunit with a decrease in the phosphorylation of both Tyr876-GluA2 and Ser880-GluA2 residues in the amygdala, and an increase in the phosphorylation of Ser880-GluA2 in the mPFC. These results demonstrate that exposure to acute stress causes subunit-specific and region-specific changes in glutamatergic transmission, which likely lead to the reduced synaptic efficacy in the mPFC and DH and augmented activity in the amygdala and VH. In addition, these findings suggest that modifications of glutamate receptor phosphorylation could mediate the disruptive effects of stress on cognition. They also provide a means to reconcile the contrasting effects that stress has on synaptic plasticity in these regions. Taken together, the results provide support for a brain region-oriented approach to therapeutics

    LMS-Verify: abstraction without regret for verified systems programming

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    Performance critical software is almost always developed in C, as programmers do not trust high-level languages to deliver the same reliable performance. This is bad because low-level code in unsafe languages attracts security vulnerabilities and because development is far less productive, with PL advances mostly lost on programmers operating under tight performance constraints. High-level languages provide memory safety out of the box, but they are deemed too slow and unpredictable for serious system software. Recent years have seen a surge in staging and generative programming: the key idea is to use high-level languages and their abstraction power as glorified macro systems to compose code fragments in first-order, potentially domain-specific, intermediate languages, from which fast C can be emitted. But what about security? Since the end result is still C code, the safety guarantees of the high-level host language are lost. In this paper, we extend this generative approach to emit ACSL specifications along with C code. We demonstrate that staging achieves ``abstraction without regret'' for verification: we show how high-level programming models, in particular higher-order composable contracts from dynamic languages, can be used at generation time to compose and generate first-order specifications that can be statically checked by existing tools. We also show how type classes can automatically attach invariants to data types, reducing the need for repetitive manual annotations. We evaluate our system on several case studies that varyingly exercise verification of memory safety, overflow safety, and functional correctness. We feature an HTTP parser that is (1) fast (2) high-level: implemented using staged parser combinators (3) secure: with verified memory safety. This result is significant, as input parsing is a key attack vector, and vulnerabilities related to HTTP parsing have been documented in all widely-used web servers.</jats:p

    Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

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    <p>Abstract</p> <p>Background</p> <p>Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D<sub>2</sub>. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D<sub>2 </sub>internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.</p> <p>Results</p> <p>We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.</p> <p>Conclusions</p> <p>Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.</p

    Building safer robots: Safety driven control

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    In recent years there has been a concerted effort to address many of the safety issues associated with physical human-robot interaction (pHRI). However, a number of challenges remain. For personal robots, and those intended to operate in unstructured environments, the problem of safety is compounded. In this paper we argue that traditional system design techniques fail to capture the complexities associated with dynamic environments. We present an overview of our safety-driven control system and its implementation methodology. The methodology builds on traditional functional hazard analysis, with the addition of processes aimed at improving the safety of autonomous personal robots. This will be achieved with the use of a safety system developed during the hazard analysis stage. This safety system, called the safety protection system, will initially be used to verify that safety constraints, identified during hazard analysis, have been implemented appropriately. Subsequently it will serve as a high-level safety enforcer, by governing the actions of the robot and preventing the control layer from performing unsafe operations. To demonstrate the effectiveness of the design, a series of experiments have been conducted using a MobileRobots PeopleBot. Finally, results are presented demonstrating how faults injected into a controller can be consistently identified and handled by the safety protection system. © The Author(s) 2012

    Striatal Pre- and Postsynaptic Profile of Adenosine A2A Receptor Antagonists

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    Striatal adenosine A2A receptors (A2ARs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D2 receptors (D2Rs). A2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A1 receptors (A1Rs). It has been hypothesized that postsynaptic A2AR antagonists should be useful in Parkinson's disease, while presynaptic A2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A2AR-D2R and A1R-A2AR heteromers to determine possible differences in the affinity of these compounds for different A2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A2AR when co-expressed with D2R than with A1R. KW-6002 showed the best relative affinity for A2AR co-expressed with D2R than co-expressed with A1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential pre- versus postsynaptic actions, SCH-442416 and KW-6002 may be used as lead compounds to obtain more effective antidyskinetic and antiparkinsonian compounds, respectively

    A Dopaminergic Gene Cluster in the Prefrontal Cortex Predicts Performance Indicative of General Intelligence in Genetically Heterogeneous Mice

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    Background: Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on selective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals ’ performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). Methodology/Principal Findings: Animals ’ general cognitive abilities were first determined based on their aggregate performance across a battery of five diverse learning tasks. With a procedure designed to minimize false positive identifications, analysis of gene expression microarrays (comprised of &lt;25,000 genes) identified a small number (,20) of genes that were differentially expressed across animals that exhibited fast and slow aggregate learning abilities. Of these genes, one functional cluster was identified, and this cluster (Darpp-32, Drd1a, and Rgs9) is an established modulator of dopamine signaling. Subsequent quantitative PCR found that expression of these dopaminegic genes plus one vascular gene (Nudt6) were significantly correlated with individual animal’s general cognitive performance. Conclusions/Significance: These results indicate that D1-mediated dopamine signaling in the PFC, possibly through it
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