Creation of dense polymer brush layers by the controlled deposition of an amphiphilic responsive comb polymer

We introduce a copolymer with a comb topology that has been engineered to assemble in a brush configuration at an air-water interface. The molecule comprises a 6.1 kDa poly(methyl methacrylate) backbone with a statistical amount of poly[2-(dimethyl amino)ethyl methacrylate] polybase side chains averaging 2.43 per backbone.. Brush layers deposited with the hydrophobic PMMA backbone adsorbed to hydrophobized silicon are stable in water even when stored at pH values less than 2.0 for over 24 h. The use of a Langmuir trough allows a simple controlled deposition of the layers at a variety of grafting densities. Depth profiling of brush layers was performed using neutron reflectometry and reveals a significant shifting of the responsiveness of the layer upon changing the grafting density. The degree of swelling of the layers at a pH value of 4 (below the pK(b)) decreases as grafting density increases. Lowering the pH of the subphase during deposition causes the side chains to become charged and more hydrophilic extending to a brush-like configuration while at neutral pH the side chains lie in a "pancake" conformation at the interface. (C) 2009 Elsevier Ltd. All rights reserved

Control of substrate access to the active site in methane monooxygenase

Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere. These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.6-kilodalton reductase (MMOR), and a 15.9-kilodalton regulatory protein (MMOB), required to couple electron consumption with substrate hydroxylation at the catalytic diiron centre of MMOH. Until now, the role of MMOB has remained ambiguous owing to a lack of atomic-level information about the MMOH–MMOB (hereafter termed H–B) complex. Here we remedy this deficiency by providing a crystal structure of H–B, which reveals the manner by which MMOB controls the conformation of residues in MMOH crucial for substrate access to the active site. MMOB docks at the α[subscript 2]β[subscript 2] interface of α[subscript 2]β[subscript 2]γ[subscript 2] MMOH, and triggers simultaneous conformational changes in the α-subunit that modulate oxygen and methane access as well as proton delivery to the diiron centre. Without such careful control by MMOB of these substrate routes to the diiron active site, the enzyme operates as an NADH oxidase rather than a monooxygenase. Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle.National Institute of General Medical Sciences (U.S.) (Grant GM 32114

2000-15 Taxes and Marriage: A Two-Sided Search Analysis

Fil: Chade, Héctor. Universidad de San Andrés. Departamento de Economía; Argentina.Fil: Ventura, Gustavo. Universidad de San Andrés. Departamento de Economía; Argentina

A xandarellid artiopodan from Morocco – a middle Cambrian link between soft-bodied euarthropod communities in North Africa and South China

NB. A corrigendum [correction] for this article was published online on 09 May 2017; this has been attached to this article as an additional file. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2017. The attached file is the published version of the article

Change escalation processes and complex adaptive systems: from incremental reconfigurations to discontinuous restructuring

This study examines when “incremental” change is likely to trigger “discontinuous” change, using the lens of complex adaptive systems theory. Going beyond the simulations and case studies through which complex adaptive systems have been approached so far, we study the relationship between incremental organizational reconfigurations and discontinuous organizational restructurings using a large-scale database of U.S. Fortune 50 industrial corporations. We develop two types of escalation process in organizations: accumulation and perturbation. Under ordinary conditions, it is perturbation rather than the accumulation that is more likely to trigger subsequent discontinuous change. Consistent with complex adaptive systems theory, organizations are more sensitive to both accumulation and perturbation in conditions of heightened disequilibrium. Contrary to expectations, highly interconnected organizations are not more liable to discontinuous change. We conclude with implications for further research, especially the need to attend to the potential role of managerial design and coping when transferring complex adaptive systems theory from natural systems to organizational systems

EEG Reactivity Predicts Individual Efficacy of Vagal Nerve Stimulation in Intractable Epileptics.

Background: Chronic vagal nerve stimulation (VNS) is a well-established non-pharmacological treatment option for drug-resistant epilepsy. This study sought to develop a statistical model for prediction of VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders. Materials and Methods: Power spectral analyses were computed retrospectively on pre-operative EEG recordings from 60 epileptic patients with VNS. Thirty five responders and 25 non-responders were compared on the relative power values in four standard frequency bands and eight conditions of clinical assessment—eyes opening/closing, photic stimulation, and hyperventilation. Using logistic regression, groups of electrodes within anatomical areas identified as maximally discriminative by n leave-one-out iterations were used to classify patients. The reliability of the predictive model was verified with an independent data-set from 22 additional patients. Results: Power spectral analyses revealed significant differences in EEG reactivity between responders and non-responders; specifically, the dynamics of alpha and gamma activity strongly reflected VNS efficacy. Using individual EEG reactivity to develop and validate a predictive model, we discriminated between responders and non-responders with 86% accuracy, 83% sensitivity, and 90% specificity. Conclusion: We present a new statistical model with which EEG reactivity to external stimuli during routine presurgical evaluation can be seen as a promising avenue for the identification of patients with favorable VNS outcome. This novel method for the prediction of VNS efficacy might represent a breakthrough in the management of drug-resistant epilepsy, with wide-reaching medical and economic implications

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex

The loss of dopamine (DA) in Parkinson’s is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1

The transition into veterinary practice: Opinions of recent graduates and final year students

Background The transition from veterinary student to member of the veterinary profession is known to be challenging. This study aimed to determine and compare the opinions of final year veterinary students and recent graduates on graduate attributes that ease this transition. Methods The study was carried out across 3 veterinary schools in the United Kingdom. Paper based or electronic surveys were used. Final year students in the 3 schools were surveyed either electronically (school A) or on paper (schools B and C). Student cohort sizes were 112, 227 and 102 respectively. Recent graduates were contacted either at a reunion event (school A) or electronically from database records (school B and school C). Cohort sizes of contacted graduates were 80, 175 and 91 respectively. Respondents were asked to rate 42 individual attributes on a 5 point Likert scale. Focus groups with final year students and recent graduates and telephone interviews with recent graduates were carried out. Data were analysed by two researchers through a combination of manual coding and thematic analysis. Data were grouped into broad themes then sorted into narrower themes. Data were then searched for counter examples. Results Response rates for final year students were 34% (school A), 36% (school B) and 40% (school C). Response rates for recent graduates were 56% (school A), 20% (school B) and 11% (school C). There was a high level of agreement between the cohorts with respect to communication skills, problem solving and decision making skills, recognition of own limitations and the ability to cope with pressure all rated unanimously important or very important. Business acumen, knowledge of veterinary practice management and research skills were the 3 attributes ranked at the bottom of the list. Nine attributes were identified with a significantly different (p < 0.05) ranking between the cohorts. Final year students ranked veterinary clinical knowledge, knowledge of veterinary public health and zoonotic issues, veterinary legislation and veterinary practice management, commitment to continuing professional development and ability to evaluate information higher than recent graduates. Recent graduates ranked the attributes of integrity, friendliness and compassion higher than final year students. Conclusions Recent graduates and final year students rate highly the attributes which help foster the client/veterinarian relationship. Recent graduates reflect that a focus on knowledge based attributes is less important once in practice when compared to final year. The study confirms the importance to recent graduates and final year students of attributes considered as non-technical in the transition to working in the veterinary profession

Detecting suicidality among adolescent outpatients: evaluation of trained clinicians' suicidality assessment against a structured diagnostic assessment made by trained raters

<p>Abstract</p> <p>Background</p> <p>Accurate assessment of suicidality is of major importance. We aimed to evaluate trained clinicians' ability to assess suicidality against a structured assessment made by trained raters.</p> <p>Method</p> <p>Treating clinicians classified 218 adolescent psychiatric outpatients suffering from a depressive mood disorder into three classes: 1-no suicidal ideation, 2-suicidal ideation, no suicidal acts, 3-suicidal or self-harming acts. This classification was compared with a classification with identical content derived from the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) made by trained raters. The convergence was assessed by kappa- and weighted kappa tests.</p> <p>Results</p> <p>The clinicians' classification to class 1 (no suicidal ideation) was 85%, class 2 (suicidal ideation) 50%, and class 3 (suicidal acts) 10% concurrent with the K-SADS evaluation (γ²= 37.1, df 4, p = 0.000). Weighted kappa for the agreement of the measures was 0.335 (CI = 0.198–0.471, p < 0.0001). The clinicians under-detected suicidal and self-harm acts, but over-detected suicidal ideation.</p> <p>Conclusion</p> <p>There was only a modest agreement between the trained clinicians' suicidality evaluation and the K-SADS evaluation, especially concerning suicidal or self-harming acts. We suggest a wider use of structured scales in clinical and research settings to improve reliable detection of adolescents with suicidality.</p